AD-RI92 655 HORMONAL REGULATION OF FLUID AND ELECTROLYTES: EFFECTS 1/OF HEAT EXPOSURE A.. CU) ARMY RESEARCH INST OFENVIRONMENTAL MEDICINE NATICK MA

UISELRSSIFIED R P FRANCESCONI ET AL. FEB 86 F/G 6110I U

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6.. NAME OF PERFORMING ORGAATION 6b. OFFICE SYMBOL 7a. NAME OF MONITORING ORGANIZATION-uS Army Research (nstitute of if applicable)Environmental Medicine SGlM.,E-HR

6c. ADDRESS (City, State, and 41P Code) 7b. ADDRESS (City, State, and ZIP Code)Heat Research DivisionNatick, MA 01760-5007

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Hormnal Regulation of Fluid and Electrolytes: Effects of Heat Exposure and Exercisein the Heat 1

12. PERSONAL AUTHOR(S)R.P. Francesconi, M.N. Sawka, R.W. and K.B. Pandolf

13a. TYPE OF REPORT 113b. TIME COVERED I'.*DAT~9RP~ (Year, Month, Day) 115. GE COUNTManuscript I FROM TO T

16. SUPPLEMENTARY NOTATION

t17. COSATI CODES 18. SUBJECT TERMS (Continue on reverse if necessary and identify by block number)'. FIELD GROUP SUB-GROUP 7Hypohydration, Acclimation, Electrolytes, Plasma Volume,

Aldosterone, Vasopressin, Plasna Renin Activity

ABSTRACT (Continue on reverse if necessary and identify by block number)

Arr extensive review has been carpleted of the hormonal regulation of fluid and electrolytebalanc.e during sedentary exposure to or exercise in the heat. The review focuses mainlyon human responses although examples from animal studies are also included. The effectsof exogenously administered hormones has been discussed followed by sections on hormonalresponse to sedentary heat exposure and exercise in the heat. Consideration of theexacerbative effects of hypohydration on the hormonal responses is followed by a sectionon electrolyte supplementation and the effects of heat acclimation. The review concludeswith a discussion of the role of plasma volume in modifying the endocrinological responsesas well as suggestions for future studies in this area. , Ke I/ ,. -I

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HORMONAL REGULATION OF FLUID AND ELECTROLYTES: EFFECTS OF HEAT EXPOSURE

AND EXERCISE IN THE HEAT

R.P. Francesconi, N.N. Sawka, R.W. Hubbard and K.B. PandolfUS Army Research Institute of Environmental MedicineNatick, Massachusetts 01760-5007

INTRODUCTION

A review of the endocrine factors which subserve fluid and electrolyteregulation during acute or chronic sedentary heat exposure or during exercisein the heat necessarily focuses on two target organs - the sweat gland and thekidney. While the acquisition of beat acclimation in humans is partiallycharacterized by a striking ability to secrete increased quantities of a more

] dilute sweat (3,121,131), there are relatively few studies in the scientificliterature describing the direct hormonal control of sweat secretory rate,composition, or total output. Further, studies which have reported thesedirect effects of exogenously administered hormones (e.g. aldosterone,angiotensin I or II, antidiuretic hormone or vasopressin) on sweat glandactivity provided, at best, inconsistent results with various investigatorsreporting increased, decreased, or no effecti on sweat secretion.

Effects of Exogenous Hormones

In an attempt to confirm the responsivity of the eccrine sweat gland toantidiuretic hormone (vasopressin, VP) stimulation, Fasciolo et al. (48)injected VP subdermally at 3 sites (forearm, abdomen, thigh) in 6 malevolunteers and collected sweat samples for three 40 min periods at each siteand the contralateral control area. Sweating was induced by heat exposure orMecholyl administration, and the results indicated that, indeed, sweatsecretion was generally reduced by VP treatment; moreover, the sodium (Na#)concentration of the sweat was increased, and these investigators concludedthat VP had a direct effect on sweat duct permeability and water reabsorption.

In a very early experiment Ladell (109) Injected deoxycorticosteroneacetate intramuscularly in acclimated subjects and collected forearm sweatduring work in a hot environment. The results indicated that the hormone,acting directly on sweat gland secretion, elicited a 30% reduction in thesodium chloride (NaCl) content of the sweat. At approximately the same timeConn et al. (29) also administered deoxycorticosterone acetate to men before,during, and after acclimation to heat, and reported that the concentration ofNaCl lost in sweat was significantly lowered and that cessation of hormonaladministration promptly resulted in increased salt losses even in acclimatedsubjects. In fact, they concluded that the exogenous administration ofhormone repressed endogenous mineralocorticoid secretion, and full recoveryfrom this hyposecretory activity required several days.

Twenty years later Collins (24) administered d-aldosterone at 6 hintervals and induced sweating by intradermal injection of methacholine. Hereported that between 12-30 h following the first aldosterone injection, the

88 3 18 049 - -

sodium/potassiua ratio was maximally depressed, urine flow and sweat secretionwere both attenuated, and 2 days were necessary for these variables to returnto normal levels after the final Injection of aldosterone. These studies ledBraun et al. (18) to administer d-aldosterone exogenously to young, healthyvolunteers in an attempt to accelerate the acquisition of heat acclimation.They concluded (18) that while the total time necessary for full acclimationwas not reduced, performance time was Increased while mean rectal temperatureand heart rate were reduced during the first several days of exercise in theheat.

In other related studies Gibinski et al. (69) administered 1.25 mgaldosterone acetate or 0.5 and 1.0 g Aldactone (spironolactone) beforeexposure to a hot, wet (480/400C, db/wb) environment and measured severalsweat variables during the heat exposure. They (69) observed no effects ofeither intervention on sweat chloride, sodium, and potassium (K). Whileurinary Na/K ratios were decreased by heat exposure and heat exposure plusaldosterone administration, the antagonistic effects of Aldactone onaldosterone prevented Na conservation and urinary Na/K ratios were unaffected(70) in this trial. Since Aldactone affected urinary sodium conservationwhile sweat sodium concentrations were unaffected by this treatment, theseworkers concluded that the mechanisms of action in the sweat glands andkidneys 'differ entirely'.

When Zgoda et al. (168) exposed 10 test subjects to 490C for 2 h/d for 5 dand administered VP intranasally to 5 subjects daily, they reported that theVP-treated group manifested decreased rectal temperature (Tre) and heart rateduring the heat exposure. In a related paper (11) a 10 min work interval wasadded at the conclusion of the 2 h heat exposure, and they observed no effectson sweat rate while 'psychophysiological' improvement was noted in subjectsreceiving Ihe peptide. Senay and van Beaumont (153) injected vasopressin(Pitressin ) intramuscularly before a final hour of heat exposure with waterreplenishment and observed no effects of VP administration on evaporativewater loss while urinary water loss was reduced in both subjects. Ratner andDobson (127) had earlier reported that VP administration and heat exposureelicited a marked increase in urinary osmolality with no changes in sweatosmolality. In a more recent paper Gibinski et al. (71) also administered VPto a group of volunteers and observed no effects on sweat rate, osmolality,and electrolytes. In the latter experiments (71) no effects on urineosmolality were reported. Thus, despite a significant number ofinvestigations, uncertainties persist with respect to the effects ofexogenously administered hormones on the volume and chemical composition ofboth sweat and urine.

Clearly, these sometimes divergent observations, especially with respectto exogenous VP, underscore the fact that the control of fluid and electrolytebalance in higher organisms is an extremely complex and exquisitely controlledsystem involving certainly not only hormonal, but also neural and otherphysiological factors (106). This topic has been the subject of frequent andextensive reivews and is well beyond the scope and intent of the current paper(For general reviews see: 9,13,81,97,128). In addition, there are severalearlier reviews available which readers might wish to consult concerning waterand electrolyte balance and metabolism during sedentary or active exposure tohot environments (23,28,46,80,112,166). Although Doucet (40) has recentlynoted that there are over 20 hormones controlling kidney function andregulation, most of these have not been investigated for their potentialimpact in controlling fluid and electrolyte balance during heat exposure.

Generally, it has been concluded that sedentary exposure to or exercise ina hot environment for at least 1 h by non-acclimated individuals without fluidreplenishment is usually accompanied by a reduction of the interstitial andplasma volumes (56) and a significant loss of Na+ in sweat (100).Additionally, blood flow is redistributed from the visceral circulation

~. .. /

(135,136) to the exercising muscles or skin surface for heat dissipation. Theearly decrements in plasm volume (83) and renal blood flow (143) stimulatethe activity of the renin-angiotensin system (47,52) as well as the synthesisand release of aldosterone (34,37) (Fig.1). If a heat/exercise regimen ismaintained for at least several consecutive days, stimulated aldosterone (A)and vasopressin (VP) secretion will effect precipitous declines in urinaryvolumes (23,46) in euhydrated and, especially, hypohydrated individuals andNa+ excretion in the urine (62) followed soon thereafter by significantdecrements in sweat Na+ (12). Because of the marked reductions in sweat andurinary Na+ loss, Na+ balance may be rapidly re-established even in thepresence of only moderate levels of Na+ consumption, and this may contributeto the beginnings of plasm volume (PV) expansion associated with heatacclimation.

If daily exercise in a hot environment persists, water and electrolyteequilibrium Is usually fully re-established after approximately 1 week of theexercise/heat regimen (6) as long as fluid and electrolyte replacement isadequate. Certainly by this time sweat and urinary Na+ losses have beenminimized even while sweat volume has been significantly increased (160),urinary output Is adequate but attenuated, and resting PV may be expanded overa broadly reported range, e.g. 7% (15), 15% (85), and 23% (147) while totalbody water may be expanded by approximately 6% (32). The magnitude of thehormonal responses and adjustments which help to maintain fluid andelectrolyte balance during acute or recurrent sedentary heat exposure orexercise In the heat may be affected by the acclimation (or training) statusof the Individual, the hydrational status, the nutritional status (expeciallywith respect to electrolytes), the duration and intensity of the stress, aswell as additional variables which may be introduced by the actualexperimental scenario. In this chapter we will attempt to consider each ofthe Important factors relevant to the hormonal control of or the hormonalresponse to electrolyte and fluid perturbations during sedentary or activeexposure to heat stress.

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after 30 min intermittent 0;uro to a hot bath (400C), and the final tmnplt(W13) during the final minute of 10 min wontintois exercise an a bicycleegameter (40*C, 751). 1e rest intarfal, hot bath, and ecercise period Wecontlguous. The blood savla we taken on alternate daya during an 11 dbeat aoclimation Program. Nm values ftr G yug adult males ae depictd.. but on/Results of this study eqtAsige the iqsortance of exercise ( 3), vith its biilty Cadge

encurrent diversion of blood flac from the vlscera, in gtimulating thebiosynthesis and reducing the clearance of Pm an 1. (Pidrawn fram: cavim Avail and/orat al., J. Av. Phsiol.. 50, 605, 1001 with Pmssion of the piblisber) Speolal.Seia

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Fitg. 2 MfecU atsfItne hat (85-.90o) an plam zw~n activity -adaldonterne :Leels to 6 hedthy adht sela too were aqw rumn 4 uns nows.Mom val---+ IMt we depleted. Vene blcod smles vwr taken at the tims=*Aed %bile ubjects ramained saftnts-. h rpdty, of the Mq tespaselnittte the hwortance of di~ac Ca bloWd ftl frm the refnal bed InInc~raming lP the greaer (4X) reelpwne of 1PA my IM11cate the genwlizaadranoaiotrcph effect. (ftftawn ,rans F z at al., .AlMmol, 41, 323, 1976 with pumission at the p )

SEDENTARY HEAT EXPOSURE

: Perhaps the most rapid sedentary exposure to heat stress eliciting

significant alterations in hormones controlling plasma volume was reported by~a Helsinki group using conditions "typical of a Finnish sauna bath". Kosunen

et al. (108) and Adlerkreutz at al. (2) reported the hormonal responses ofexperienced sauna users to 20 min exposure at 85-900C. Their resultsindicated that just 10 min after exposure to the intense heat stress, levels.of plasm renin activity (PRA) and angiotensin 11 were significantlyincreased; increments in plasma aldosterone (PA) levels were delayed until 20min after exposure with even greater elevations observed 0.5 h aftercompletion of the heat stress. Generally, hormonal levels had returned tocontrol ranges 6 h following heat exposure (Fig. 2).

These extremely rapid hormonal responses suggest that fluid shifts and -shifts in blood flow-cardiac output distribution are stimulatory to %

endocrinological responses in the absence of notable fluid loss. Rowell (134)has estimated that skin blood flow can be increased to 7-8 L/min during severebeat stress, and concluded that splanchntc vasoconstriction was initiatedprimarily by the sympathetic nervous system since increments in PRA occurconcomitantly with elevations in heart rate and plasma noreptnephrine levels.Baroreceptors my be initially involved followed by the activation of volume,osmo-, and thermoreceptors as the stress persists elicitting plasma volumedecrements, osmolaltty increments, and elevations in core temperature.

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Dumoulin at i. (41) used an 800C environment and 20 min exposure time toeffect significant elevations in both PRA and PA. In their earlier reportKosunen et al.(108) indicated that no changes occurred In PV as estimated fromhematocrit, hemoglobin, and plasm protein (PP) values. The rapidity of thehormonal changes In these studies Is noteworthy; just 10 min after Intenseheat exposure, circulating Indices of fluid and electrolyte conservation andsplanchnic and renal vasoconstriction were evident. The spontaneity of theseresponses suggests that Increased circulating hormonal levels can be elicitedby reduced hepatic and renal clearance In addition to accelerated biosynthesisof these hormones. Collins et al. (26) have reported that the metabolicclearance rate of aldosterone was reduced from 77 LIh to 57 Lih when deep bodytemperature was raised by 1.080C. The effects of acclimation on the clearanceof fluid and electrolyte regulatory hormones have not been assessed (25).

Rocker et al. (132) extended the heat exposure (70-75oC) to 4 h with a 10min interval at 19-21OC during each hour. With no fluid replenishment thistest scenario affected a dehydration of 2.4 kg or 3.4% of pre-exposure bodyweight. In addition to observing a 100% elevation of plasma vasopressin (PYP)at the end of the heat exposure, which was further increased to approximately160% 90 min later, they also reported significant increments in plasmaosmolality and concomitant decrements in plasma volume, thus emphasizing theimportance of the duration of the stress In affecting physiological responsesand the impact of fluid loss in addition to fluid shifts in eliciting markedhormonal elevations. Earlier, these workers had employed the sameexperimental protocol (133) to show that untrained women manifested smallerreductions in plasma volume than men.

While sedentary exposure to sauna temperatures thus elicited rapid andintense alterations in circulating hormone levels when large shifts In fluidvolumes and blood flow distribution were occurring, much of the experimentalwork in humans as well as higher animals has been accomplished under muchlower ambient conditions. Szczepanska-Sadowska (161) used pre-implantedthermodes near the pre-optic area of dog forebrain to raise brain temperatureby 1.50C in the absence of generalized heat stress and remarkably observed 10-fold elevations in circulating VP levels just 10 min after heating. Eismanand Rowell (43) exposed 6 male baboons to environmental temperatures rangingfrom 42-490C and observed 24% reductions in renal blood flow per OC rise incore temperature giving rise to 98% increments in PRA per oC elevation. Thissame group of investigators would later (47) use human subjects in water-perfused suits to show that raising Tre by 10C elicited increases In PRA of135% and in splanchnic vascular resistance of 73%. B-blockade, induced bypropranolol administration, reduced PRA, but elevations in splanchnic vascularresistance were less affected. These investigators speculated (47) that whilePRA is effective in eliciting visceral vasoconstriction when heat stress ismild, increased stress Intensity may stimulate sympathetic nervous system-induced vasoconstriction. Rowell (134) later hypothesized that angiotensin I1may have more marked effects on the renal vs the splanchnic circulation.

Thus, in the absence of exercise, exposure to heat stress is accompaniedby reduced urinary fluid and electrolyte loss partially under the influence ofincreased PRA (43,47,49) and aldosterone (49,55). Simultaneously, cutaneousvasodilation, occurring In humans generally over the entire surface of thebody from the lower extremities to the cheek and ear region (148), permits theincreased peripheral blood flow provided by the enormous increments in cardiacoutput which results in similarly increased evaporative, radiative, andconvective heat loss under appropriate conditions. Of course, in the passivemode the absence of increased metabolic heat production from muscular activityresults in comparably lower sweat rates to maintain thermal equilibrium underspecified conditions of ambient temperature and duration of exposure.

Elizondo et al. (44) used an envirnmental temperature of 36-40oC toinduce sweat rates of up to 0.65 mg/cmi/min, and reported that while sodium

concentration (Na) increased with Increasing sweat rate, the potassium

concentration (K) of the sweat was reduced. These investigators (44) usedlocal skin heating (to 42C) and arterial occlusion to increase or decrease,respectively, sweat output, but did not speculate on the control ofelectrolyte loss in the sweat. Harrison (82) Investigated the effects of 2 hsedentary exposure to 480C, and observed that while plasma Na and K+ wereunaffected, there occurred a linear decrease of water from the intravascularspace which could be correlated with either increasing hematocrit or proteinconcentration. Additionally, van Beaumont et al. (164) used similarconditions (sedentary, 45C, 3 h) to demonstrate that thermal dehydration(1.9% loss In body weight, bw) was accompanied by proportionately greaterreductions in plasma volume (5.9%) than heat stress alone. Theseinvestigators (164) concluded that the dynamics of hemodilution andhemoconcentration during sedentary heat exposure may be related to the onsetof sweating, initial sweat rate, and total sweat loss.

To this point, the results from studies using initially euhydrated humansubjects in climatic chambers, sedentary exposure to heat ranging frommoderate to intense, and durations ranging from a fraction of an hour toseveral hours indicated that hormonal adjustments conducive to fluid andelectrolyte conservation are generally rapid and consistent. Surprisingly,Candas et al. (20) showed that marked hidromelosis (reduction in sweat ratedue to skin wettedness with prolonged sweating) during repeated exposures tohot, humid conditions did not elicit any changes in PA, PRA, or PVP. Duringactive heat dissipation in the passive mode, visceral blood flow is attenuatedand the peripheral share of cardiac output is increased to as much as 60% ofthe total (134). Despite the hormonal adjustments designed to conserve fluidand electrolytes, dehydration may occur and plasma volume may be noticeablyreduced if fluid replenishment is inadequate or heat stress is intense andprolonged.EXERCISE IN THE HEAT

When physical exercise Is added to the stress of the hot environment, thenthe cascade of endocrinological and physiological adjustments necessary tomeet metabolic and thermoregulatory demands is increased. When we exercisedrats in the heat (350C) and removed a blood sample for analysis when Trereached 400C, we observed significant elevations in PA in this sample whichwas taken just 8.25 min (mean) after the initiation of exercise (61). Inhumans increased cardiac output and blood flow to sustain the metabolicdemands of the working muscles must be partially distributed also to the skinsurface for sweat secretion and evaporation; the percentage of cardiac outputto each may be determined by the work intensity and the ambient temperature.In any event, the surfeit of deep body heat, which can raise core temperaturesto injurious levels, must be transferred to the periphery for radiative,convective, or evaporative dissipation. To meet the enormous demands placedupon the cardiovascular system during exercise in the heat (120) in man oranimals, plasma volume must be protected and sustained. Fortunately, healthyhumans ordinarily possess physiological and endocrinological mechanisms todefend plasma volume, reduce electrolyte loss, promote heat loss, andattenuate physiological strain during work in the heat.

Even at apparently moderate, but unspecified, environmental temperatures,

Convertino et al. (30) observed that increasing the workload (bicycle-ergometer, 100, 175, 225 watt, W) among 15 healthy male test subjects elicitedlinear (with workload) increments in PRA which were significant at all threework intensities. Circulating VP, however, manifested a more curvilineurincrease which was markedly elevated at the highest work load. Decrements inplasma volume were also linearly (inversely) correlated with workload (-3.7%at 100 to -12.4% at 225 W). While changes in circulating Na concentrationand osmolality were closely correlated with changes in VP, these variableswere not correlated with PRA. These results indicate that PRA responds

linearly to the reduction in renal blood flow due to the diversion of cardiac'output to the exercising muscle mass. However, PVP release may be moreclosely correlated with elevated osmolality and plasma sodium levels. Whenthe same group of investigators (31) later studied the effects of training onthe responses of many of these same variables at an ambient temperature of250C, they reported that training increased resting PV by 12.3% althoughresting baseline levels of PRA and PVP were unaffected by training. Further,they demonstrated that the increments in PRA and VP during exercise observedprior to training were attenuated by the training regimen. The effects oftraining on plasma protein concentrations and total circulating protein werenot evaluated. It is noteworthy that, subsequent to training, the percentagedecreases in plasma volume were reduced following 175 W and 225 W exercise(31) since total PV was increased by the training regimen. Also, because ofthe increased V02 max (11.2%), each workload represented a lowered relativeintensity (% V02 max) and therefore a decreased physiological strain on thetest subjects. This is certainly suggestive evidence that the magnitude ofthe response of the fluid regulatory homones may be affected by the relativeexercise intensity and the plasma volume itself.

Interestingly, when Finberg et al. (52) compared the responses of adultmales to walking in the heat (level treadmill, 1.3 m/s, 90 min, 500C) duringthe summer and winter months, they observed again an attenuated response ofPRA during the summer trial which may be related to the increased plasmavolume of natural acclimatization during the summer months. They alsoreported (52) that replacement of the estimated fluid loss during the 90 minwalk with water and NaCl reduced the intensity of the PRA response pattern in4 out of 5 subjects (Fig. 3), thus indicating probably that fluidreplenishment helped to sustain renal blood flow, albeit at reduced levels.When Costill et al. (33,34) used exercise (60 min, 60% V02 max) at 300C tostudy urinary sodium loss, they observed that levels of PRA and PA wereelevated during and immediately following exercise in the heat, and returnedto control levels usually by 6-12 h following exercise completion.Additionally, they reported that this scenario consisting of a single exerciseinterval was effective in reducing urinary Na+ and Cl- concentrations for upto 48h, presumably due to the effects of the single elevation in PA levelssubsequent to exerit_$.e..

II

fiPg. 2 N~fets of natural acclimtization and "it replacement an the

voluntees. Individual data are depicted. In each section prs-valuss (an theleft) are ownacted to post-values (an the right). Suna trials weorndacred In ISeptwober and October thilea winter tests were executed inDobuand January. Salt Ingestion was based an the esimate that the uat1cotent of rweat lost was 400 mg100 al, and relpla'ed at is adn intarvaisduring the 90 min walk at 4.7 km^h. The Increaed intravascular volume asurm usy blunt the PM response In € nqwlson to the winter trial as thePJcl Ingestion relieves the dwmrd to repisce the us1 lost :in Mint. {IpedrawfV=1 Firnr et al., J. AMI. Phtsiol., 36, S19, 2374 with pamission of thepublisher)

Similarly, when Orenstein et al. (122) exercised normal young adult testsubjects at 50% V02 mx at 370C, also for 90 min, they observed significantelevations In PRA and PA immediately subsequent to exercise, and theseincrements contributed to marked reductions in urinary Na+ loss with noeffects on serum Na+. Alternatively, In these studies (122) cystic fibrosispatients manifested normal hormonal responses to heatlexercise stress andsimilar reductions in urinary Na+, but serum NO+ levels were also reduced,probably due to excessive loss in sweat. Interestingly, the cystic fibrosispatients, who can and do manifest the physiological advantages of heatacclimation (123) yet respond to heat stress with an Increased loss of sweatNa+ and CI- (122), thus demonstate normal responses to exercise in the heatwith respect to PRA and PA.

Therefore, during exercise in the heat hormonal responses directed atfluid and electrolyte conservation are rapid and intense with probablepersistent effects, and may be partially responsible for the defense of bodywater and extracellular fluid which help to maintain the efficiency of thecardiovascular and thermoregulatory systems. In one of the very few studieswhich has quantitated fluid- and electrolyte-regulatory hormone levels afterheat injury, Aarseth et al. (1) observed significant elevations in PRA and PVPat rest following incurrence of the injury in 6 athletes who sufferedheatstroke with Tre in excess of 42.0oC.

When humans exercise in the heat even for relatively brief Intervals,thermal sweating without fluid replacement is accompanied by generaldecrements in body weight with proportionately more intense reductions inplasma volume. Diaz et al. (38) investigated the effects of posture on plasmavolume changes during rest (45 min) and exercise (45 min) in a hotenvironment. Subjects worked on a bicycle ergometer (30% and 45% VO max,49.50C), in the upright, low-sit and supine postures without fluidreplacement. During the total heat exposure, plasma volume was reduced by 20%in the upright, 16.1% in the low sit, and 13.3% In the supine positions withno differences noted between work loads. Body weight was reduced by only 1.3-1.4% in these experiments, thus eliciting substantial ratios in the percentdecrease in PV versus percent decrease in body weight. No effects of posturewere noted on either plasma protein levels or osmolality suggesting anisooncotic and isoosmotic fluid shift out of the plasma space, and,unfortunately, hormonal responses were not assessed.

When Harrison et al. (86) exercised adult unacclimated males for 50 min at420C and 3 months later at 300C using the same experimental protocol withoutfluid replacement, they observed decrements in plasma volume of approximately10-12% by the end of the exercise period in the fluid deprivation experiment.However, during a sedentary 50 min recovery period PV recovered to control ornear control levels (depending on the method of calculation). Theseinvestigators (86) concluded that, as proposed by Senay (144, 145), the returnof protein to the intravascular space via the lymphatic system during exerciseand probably also during recovery contributed to an elevated oncotic pressure.This osmotic force in turn promotes water influx into the intravascular spaceat the expense of other fluid compartments. The same group (83) used radio-iodinated serum albumin to confirm that, following exercise, protein wastransferred to the intravascular space more rapidly than it was lost throughcapillary permeability.

Senay and Fortney (149) compared the responses of untrained females toexercise (ergometer, 30% V02 max) at 16-200C and 450C and observed a PVdecrement of nearly 13% in the thermoneutral environment and nearly 18% in theheat. While plasma protein increased markedly during the thermoneutral trial,no such increment was observed during the heat trial. This led Senay andFortney (149) to conclude that the increased perfusion and, perhaps,permeability of the cutaneous capillaries, far more extensively perfusedduring exercise in the heat, counteract the retention or accumulation of

* M

intravascular protein during the heat/exercise regimen. When Greenleaf et al.(76) used 45% V02 max and 400C Ta as an exercise/heat stress, they observeddecrements in PV of approximately 11% after 60 min. Thus, It is clear that,despite the hormonal responses which favor fluid and electrolyte retention,plasma volume Is nonetheless decreased during acute heat/cycle exercisestress. When such loss of body water results in frank hypohydration, then thephysiological and endocrinological adaptations conserving fluid andelectrolytes become even more crucial to the prevention of heat/exerciseinjury (1) and maintenance of physical performance (5).

The results indicate that passive heat exposure, exercise, and exercise inthe heat are all rapidly and variably stimulatory to increased circulatinglevels of PRA, PA, and PVP. PRA may be stimulated most effectively by areduction in renal blood flow secondary to increased muscle or skin bloodflow. PA apparently may be initially elevated by generally increasedadrenocorticotrophic activity secondary to exercise/heat stress while PVP,initially elevated by acute heat exposure or exercise heat stress, may be moreseverely affected by increased plasma Na+, osmolality, or decreased plasmavolume secondary to hypohydration.

HYPOHYDRATION

For those readers interested in the comparison among species, the apparentuniversality of the endocrinological responses to heat/hypohydration has beenconfirmed in a wide range of experimental animals. For example, Keil andSevers (98) observed in rats that 48 h of water deprivation was effective ineliciting marked elevations in plasma vasopressin levels, but these incrementswere attenuated with increasing weight of the experimental animals. Further,they reported (98) that the imposition of a non-thermal secondary stress(ether, acceleration) tended to reduce the elevations in PVP effected byhypohydration. Kenyon et al. (99) observed that when I ug/d of aldosteronewas administered to adrenalectomized rats, the animals produced a small volumeof more concentrated urine and plasma K+ levels were increased. When ratswere passively exposed to an ambient temperature of 400C, PVP levels wereincreased and the increments were surprisingly exacerbated by propranololtreatment (77). Arad et al. (4) examined the hormonal, fluid, and electrolyteresponses in domestic fowl and noted that hypohydration (13% bw, 48 h waterdeprivation) increased PA, PVP, Na+, and osmolality, all of which wereexaggerated when hypohydration was combined with heat exposure (final ambientm42C) and attenuated during a rehydration interval (30 min); however, heatexposure alone had no effects on these variables. During hypohydration andheat exposure, core temperature increased to 43.70C from 42.80C (heat alone);similarly, plasma osmolality increased from 319 to nearly 360 mosm/kg,respectively.

Interestingly, Thrasher et al. (163) reported In dogs that 24 h of waterdeprivation (. 5% body weight loss) caused significant elevations in Na+,osmolality, PVP, and PRA which had returned to control levels after 1 d ofrehydration. Alternatively, PA was not significantly affected duringdehydration, but peaked at 24 h of recovery. They (163) attributed this 24 hpeak to a decrement in plasma Na+ occurring upon rehydration which wascountermanded by this PA response, and hypothesized that a natriuresis duringhypohydration helped to reduce the magnitude of the increments in plasmaosmolality. However, using hyperhydrated goats Augustinsson et al. (8)reported no increments in excretion of VP and a decrease in PA during acuteheat exposure (450C); they attributed these observations to the significantrespiratory alkalosis which developed by 60 min in this species.

Finally, even in animals as large as domestic cattle, El-Nouty et al. (45)reported that acute (8 h) heat stress (350C) elicited a mean elevation in Treof 20C and a significant elevation in PVP which was further increased whenwater was withheld for 30 h. During 24 h of heat exposure PA levels were

significantly depressed In these experiments (45), and recovered towardcontrol levels during dehydration. Again, they attributed the decrement in PAto the increased plasma Na observed during heat stress. Thus, although the -responsivity of the plasma hormones to hypohydration has been validated in awide range of experimental species, the vast majority of this research hasbeen accomplished using human test subjects.

In humans the effects of hypohydration during heat exposure and exerciseIn the heat have been extensively documented. Even In well heat-acclimatedsubjects, Strydom and Holdsworth (159) observed that during work in the heatincreasing severity of hypohydration (3-5% and 5-8% body weight decrements)caused exaggerated increases in rectal temperature and heart rates while sweatrates were reduced. In these studies optimal performance (i.e. minimalphysiological strain) was observed when test subjects were compelled torehydrate at 15 min intervals; it is generally believed that completerehydration, even when palatable and potable fluids are conveniently availableand drinking Is encouraged, is ordinarily delayed during and immediately afterexercise in the heat - a phenonemon termed voluntary dehydration (74).

The increased physiological strain of hypohydration partially results fromthe significant decrements in PV and increases in osmolality which usuallyoccur concomitantly with hypohydration, resulting in decreased sweat rates andreduced skin blood flow (138). For example, Saltin (138) observed thathypohydration, elicited by thermal exposure to a 5.2% reduction in bodyweight, may be accompanied by reductions in plasma volume by as much as 25%.He (138) further noted that the decrements in PY were accompanied bysignificantly reduced endurance capacities and maximal blood lactate whilecardiac output may be maintained by increased heart rate. Costill and Fink(36) compared the effects of thermal- and exercise-Induced hypohydration, andreported that at 4% body weight loss PV was reduced by 16-18% subsequent toeither form of dehydration. In our own experiments induction of hypohydration(3-7% body weight) is ordinarily followed by a period (12-16 h) of inactivitybefore experimentation during which fluid is redistributed to the plasma, yetPV's consistently decrease by 5-15% (139-141).

When we dehydrated men by 5% bw, we observed significant elevations in PRAand PA in blood samples taken prior to exercise; subsequent exercise in theheat reduced PV even further and PRA and PA were enhanced during hypohydrationtrials while the increases in PRA were modulated by acclimation (64) (Fig. 4).In a more recent study (65) in which we reported the effects of 3,5, and 7%hypohydration on circulating hormone responses, we observed that increasingthe intensity of hypohydration from 3% to 5% was usually accompanied by anincreased elevation in PRA and PA; however, between 5 and 7% hypohydration,where no further decrements in PV were observed (141), we likewise noted noadditional increments in either PRA or PA (Fig. 5). Consistent with theseresults Von Ameln et al. (165) demonstrated that, following thermaldehydration, PVP increased from 2.1 to 8.1 pg/ml, but this elevation wasattenuated to 4.7 pg/ml by head-out water immersion. They attributed thisattenuation of PVP response to "central hypervolemlia effected by waterimmersion.

When the same group (101) examined the effects of hypohydration induced byprolonged exercise (27-32 km) on PRA, they reported that four-fold increasesin PRA levels 50-60 min after the completion of exercise were reduced tonearly control levels about I h later and following food and fluidconsumption. In a separate experiment (16) subjects were exercised in theheat (340C, 85 W, 4 h) with no fluid replacement, with water replacement, andwith NaCl-sucrose consumption (Fig. 6). During the exercise interval levelsof PA, PRA, and PVP were progressively increased during the "no fluid' trial;however, with either water or NaCl-sucrose replacement, increments in PRA andPVP were abolished. While water consumption attenuated the increment in PAelicited by no fluid replacement, NaCl-sucrose blunted this response evenfurther, and after 4 h of exercise in the heat, levels were not different fromcontrols.

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EXERCISE INTERVALPig. 4 Effects of hyptdration (5% bw) id aclimation an plam zeninactivity ard aldosterone levels during exercise (four 25 min/LO mn work/r stcycles, level treamil, 1.34 /see) In the ht (490C, 201 tb). HMn lovels

L+ M aredeicted flor I young adult male and! I young adult fenuie tsbjects. 3K10 was taken prior to and approximtely 15-20 mi lInto the lat,

d, aMi 4th exercise Intervals. The Increased plama volue of accliation Kyhelp to maintain renal blood flow and repress the M response. fte effectsof hypohydration are mnet notable pre-accllmation (tims 0). mrawn froa:1ra ,scasd et al., 7. 1lp1. Physiol., 55, 1790, 1983 with penuisaion of thepublisher)

Thus, the evidence seems to favor strongly a rapid and marked elevation In S

circulating levels of fluid- and electrolyte regulatory hormones whenheat/exercise exposure induces progressive dehydration or a targeted level ofhypohydration precedes the heat/exercise exposure. These responses may be Irelated to Increased osmolality, decreased plasma volume, or perhaps decreasedblood pressure. While the responses of PVP and PRA have been consistent andunidirectional, there is some evidence that the control of aldosterone _secretion may be superseded by the increasing Na+ concentration which also mayaccompany hypohydration. In fact, reports on the influence of electrolytesupplements during heat exposure and exercise in the heat, the effects of "prior high or low dietary consumption of electrolytes, and the experimental 'depletion of electrolytes provide a framework to investigate further themechanisms and control of hormonal responses to heat/exercise stress.

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When Smiles and Robinson (157) examined the effects of recurrent exerciseIn the heat (100 min, 1.58 m/s, 450C) on young adult males in negative saltbalance induced by dietary manipulation, they reported 3-6 fold increments in24 h output of urinary tetrahydroaldosterone; this was accompanied by apparent10-20-fold reductions in urinary Na+. When the same experiments were repeatedwith the subjects in positive salt balance, both urinary tetrahydroaldosteroneand Na+ were at control levels suggesting that the magnitude of the sodiumconservation response during acclimation is dependent upon exogenous Na

*0 availability. Shortly thereafter, Bailey and co-workers (10) placed 12 youngadults males on high (>300 mEq/d), normal (182 mEq), and low (12 mEq) Nadiets during 3 consecutive weeks. Following the normal and low dietaryintervals, heat stress was induced by sedentary exposure to 46-510C ambientconditions and PA and PRA were assessed before and after the heat stress. Thelow-Na+ diet elicited significant increments in both PA and PRA in the pre-heat samples, and the heat exposure increased the levels of both hormonesfollowing either dietary regimen though the elevations were more notableduring the low salt trial. Interestingly, they noted that packed cell volumeswere unaffected by thermal stres, and concluded that high thermal stress, perse, is a potent stimulator of renin and aldosterone secretion. In fact, theseworkers suggested that the level of heat stress elicited by sedentary exposureto approximately 500C might be utilized as a marker of the normal response ofthese endocrine systems (10).

Recent results have generally indicated that exogenous salt loading doesnot markedly enhance the acquisition of acclimation or reduce thephysiological strain of work in the heat. Although Armstrong et al. (6)observed several sporadic advantages to consuming a high sodium diet duringacclimation to heat, Konikoff et al. (107) reported that salt supplementationin fully acclimated subjects provided no benefits during work in the heat

while PA levels were repressed and PRA was unaffected. Earlier, Follenius etal. (54) had demonstrated that consumption of a low salt diet inducedsignificant increments in basal levels of both PA and PRA; when these subjectswere acutely exposed (90 min) to sedentary heat stress, the percent increasesin PA and PRA were similar in subjects consuming either a high salt (200mEqNa/d) or low salt (20-30 mEqNa/day) diet. The same group (17) usedpropranolol to illustrate a dissociation between the responses of PA and PRAto heat stress in that propranolol reduced the PRA response to heat exposure bwhile PA was actually increased during the propranolol trial. We haveobserved dissociations in PRA and PA responses previously In both rats (57)and, under certain conditions, humans (65).

Likewise, when studying rehydration with a glucose-electrolyte solution orwater, Costill et al. (35) concluded that, following dehydration to 3% bodyweight on 5 successive days, the glucose-electrolyte drink did not provide anyphysiological benefits to the test subjects. The authors cautioned, however,that electrolyte balance was being maintained by adequate dietary consumption.In fact, they hypothesized (35) that the supplementary Na+ Intake may haverepressed PA secretion causing more Na+ and fluid loss during the glucose-electrolyte trial. In addition, Nielsen et al. (119) recently reported nosignificant effects of rehydration with a control, high potassium, highsodium, or high sugar beverage; interestingly, they concluded that the highNa+ drink specifically benefitted the extracellular fluid compartment whilethe high K+ and high sugar drinks augmented intracellular fluid volume. Ikawaet al. (96) had previously exposed volunteers to a sauna (65-70oC) for 30 minand during a recovery period provided either no fluids, 500 ml of an isotonicsports supplement containing Na+, or 500 ml of water. Circulating A levelswere significantly increased by the heat exposure, and were maintained athigher concentrations during the water or no-fluid experiment. The variousdrinks did not provide any advantages in reducing physiological strain withrespect to either rectal temperature or heart rate.

The evidence is weighted heavily toward the conclusion that In thepresence of consistent dietary intake of salt, excessive salt consumption orthe ingestion of salt-containing beverages does not have ergogenic effectsduring exercise in the heat or reduce the physiological cost of heat exposure.Harrison et al. (84) noted that when 1% NaCl was ingested to preventdehydration, core temperatures were higher than when water was consumed. Infact, there is increasing evidence to suggest that consumption of modest oreven low levels of salt (<100 mEq/d) is adequate to maintain electrolytebalance when the reduced dietary intake is followed by acute or prolonged heatexposure or exercise in the heat. Further, the maintenance of electrolytebalance under these conditions is dependent upon the effects of increasedendocrinological activity as manifested in consistently elevated PAconcentrations when dietary NaCl Intake is low, and reduced circulating PAwhen NaCl intake is above normal.

Several of the world's population groups are able to withstand chronicheat exposure on low salt diets (20-50 mEq/day) without apparent increasedrates of heat Injury; this is probably testimony to the exquisite mechanismsby which humans adapt endocrinologically for extremely efficient salt Sconservation. From this it may be reasonable to conclude that individuals whoare at most serious risk of developing salt depletion-induced heat cramps (14)are those who abruptly change from a high or average salt Intake to a lowconsumption concomitant with sustained heat exposure and profuse sweating. Inour experience we have observed this situation when large numbers of garrisonquartered troops are abruptly transferred to desert environments In thesouthwestern US for field training exercises.

The effects of potassium (K) deficiency upon the ability to work in theheat and the endocrinological responses to acute or chronic heat exposure havebeen less extensively studied. Ialhotra et al. (113) reported that K

deficiency can accrue even in well-acclimated individuals when exposed* sedentarily to 400C for 4 consecutive days, and, further, that this K* deficiency my contribute significantly to the development of heat injury. In

fact, during acclimation to heat it is conceivable that the loss of K in sweatas well as the conservation of sodium by the kidney with attendant K losscould contribute to cellular potassium depletion and the development of heatillness (142).

Knochel and his co-workers (103,104) have demonstrated that recurrent workIn hot enviroments may result in substantial negative K balance despite meandaily intakes of approximately 100 mEq; these investigators also observed thatboth PA and PRA, as well as urinary aldosterone were Ounsuppressed' for thequantities of Na that their test subjects were ingesting although noexplanation for the lack of suppression was offered. Alternatively, whenCoburn et al. (21) acutely exposed unacclimated, K-deficient test subjects toheat stress, they observed repressed urinary aldosterone excretion which theyattributed to a failure of plasma K to increase during heat exposure as aresult of the K depletion. Interestingly, their regimen of K depletion(producing deficits of 230-465 mEq K) failed to induce consistentthermoregulatory decrements in their test subjects. When Francis and co-workers (66,67) used either water or a potassium supplemented electrolytesolution for rehydration during exercise (50% V02 max, 120 min, 320C), theyobserved no marked beneficial effects of the electrolyte solution; PRA and PAwere significantly reduced during the electrolyte supplement experiment.Generally, the consensus has been that carbohydrate/electrolyte supplementsare unnecessary if balanced food consumption has not been curtailed (110).

When Hubbard et al. (95) used their rat model of human heatstroke (93,94)to investigate the effects of prolonged feeding (32 d) of a K deficient diet,they reported that exercise endurance was reduced by 37%, work done was

OW, decremented by 49%, and muscle K was depleted by 26%. At approximately thesame time Haldy and Muller (79) had reported, also In rats, that consumption Pof a K-deficient diet (2 weeks, 0.8 mmole K/kg) markedly reduced the abilityof excised and incubated adrenal glands to convert tritiated corticosterone toaldosterone. Since the biosynthesis of aldosterone in K-deficient rat adrenalglands could be stimulated by sodium deficiency, water deprivation, andfurosemide treatment, these authors concluded (79) that enzymes regulating thefinal steps in the biosynthesis of aldosterone may be instrumental in thecontrol of PA levels and inhibited by potassium deficiency.

* -In his review Knochel (102) concluded that K deficits may be associatedwith postural hypotension and syncope, reduced muscle membrane integrity, andthe development of rhabdomyolysis. While frank intracellular hypokalemia willclearly predispose an individual to increased risk of heat injury, otherpotential sequelae of acute or chronic negative K balance have not been 5

assessed in carefully controlled human studies. Interestingly, in our studieson heatstroke in rats we have demonstrated that the intensity of circulatoryhyperkalemia subsequent to exercise in the heat was inversely correlated to -

survival time (60); conversely, rats which were able to run for prolongedperiods with the achievement of a steady-state, moderate Tre (<400C)manifested reduced circulating K levels (59). Clearly, the relationshipsbetween K deficits and surfeits and plasma volume, sweat secretion, hormonalresponses, Na balance, and the acquisition of acclimation in humans should bemore extensively described (7).

HEAT ACCLIMATION

The effects of heat acclimation on the endocrinological responses to heat Yexposure/exercise in the heat are somewhat inconsistent and variable. Whenconsidering the number and range of experimental variables which couldconceivably affect such responses, this is perhaps not surprising. For

example, hydration level, acclimation status, aerobic fitness level, exerciseintensity and type, ambient conditions, electrolyte balance, sampling time,subject posture and a variety of other experimental variables (19) could,singly or in combination, affect test results and conclusions. Of these, theacclimation state may especially provide significant variability due to therange of increments in resting plasma volume which has been consistentlyreported subsequent to heat acclimation. b

When Greenleaf et al. (73, 75) exercised (45% V02 max) 2 groups of men at23.8oC and 39.80C for 8 d, they reported that during exercise in the heat, PRAand PVP levels were increased without effects of acclimation on the restinglevels prior to or increments during exercise in the heat (Fig. 7). Likewise,when Finberg et al. (51) measured PRA and PA following exercise (ergometer,40-50% V02 max, 30 min) in the heat (50oC) for 7 consecutive days, theyreported similar PRA (9.5 + 4.4 and 8.0 + 4.7, day 1 vs. day 7) and PA (22.6 +8.5 and 25.5 + 8, day 1 vs7 day 7) levels prior and subsequent to

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the acclimation regimen. Bonner et al. (15) had earlier reported similarelevations in PA prior and subsequent to acclimation and following both asedentary and exercise interval in the heat. Davies and co-workers (22,37)concluded that an 11 day acclimation program did not attenuate the incrementsin PRA and PA observed during exercise in the heat, but prior saline ingestiondid modulate these increments suggesting the more subtle effects ofacclimation vs saline consumption on endocrinological responses. WhenConvertino and Kirby (32) observed a significant reduction in 24 h Naclearance following acclimation with no changes in resting PA levels, theyconcluded that renal sensitivity to PA may be increased during acclimation.

A short time later the same workers (100) demonstrated reductions in sweatsodium loss concomitant with reductions in PA during exercise in the heat (45%V02 max, 400C) on day 10 vs day 1 of heat acclimation. Again, theyhypothesized that the reduced PA is compensated by an elevated eccrine sweatgland responsivity to PA after acclimation. The pioneering work in this areahad been accomplished much earlier by Conn who reported that acclimation canreduce the salt lost in sweat by as much as 95% (27). Finberg and Berlyne(50) had used both natural acclimatization (exposure to summer heat) andexperimentally induced heat acclimation (90 min exercise, 500C, 7 d) todemonstrate generally attenuated responses of PRA and PA to light exercise inthe heat when compared to the responses elicited in winter or withoutacclimation. They (52) had earlier reported that not only naturalacclimatization to summer heat, but also prehydration with a NaCl solutionsuppressed exercise/heat-induced increments in PRA.

Some of our own work (64,65) had also demonstrated attenuated responses ofthe fluid/electrolyte-regulatory hormones to exercise in the heat followingheat acclimation. When Shvartz et al. (156) administered tilt-table testsprior and subsequent to heat acclimation and observed 50 and 75% decrements,respectively, in responses of PRA and PVP following acclimation, they ascribedthese decreases to the increased resting plasma volume. Alternatively, whenwe acutely expanded PV by intravenous administration of hyperoncotic albumin,we reported that during exercise (63) or at rest (58) in the heat, PA levelswere suppressed. Thus, the augmented cardiovascular stability (137, 167) andplasma volume (151, 166) of heat acclimation may combine to lessen therequirement and stimulus for the usual elevations in levels of fluid andelectrolyte regulatory hormones during heat exposure or work in the heat.

Knochel and Vertel (105) hypothesized that the development of theacclimated condition is characterized by increased aldosterone secretion andexcretion. Earlier, Fletcher et al. (53) had compared aldosterone excretionrates in residents of the United Kingdom (15-17oC) and British expatriatesliving in Kuwait (380C) and reported mean 24 h urinary aldosterone levels of8.7 and 13.4 ug, respectively. Knochel and Vertel (105) reasoned that theincreased aldosterone secretion and excretion of heat acclimation could effectexcessive urinary K loss and suggested that less vigorous NaCl replacement(especially in the form of salt tablets) may be appropriate in reducingelectrolyte disorders, polyuria, and circulatory hypokalemia.

However, since these earlier suggestions that increased aldosteronesecretion and activity may be necessary for the acquisition of heatacclimation (53,68,105), more recent evidence indicates that acclimation andaerobic exercise training (117) are accompanied by an increased sensitivityand responsivity to endocrinological effects at the sites of both centralcontrol (118,129) and peripheral effectors (32,100,151). The majority of thedata suggests that subjects who are fully heat acclimated respond to heatexposure/exercise in the heat with similar or attenuated levels of PVP, PA,and PRA when compared to their non-acclimated counterparts. Such responsesappear to be consistent with the increased plasma volume, decreasedphysiological strain, increased perfusion of viscera, and electrolyte balanceassociated with heat acclimation.

PLASMA VOLUME "l A.

The thermoregulatory and cardiovascular advantages of Increased plasmavolume and total body water in reducing the physiological strain of exercisein the heat have been investigated and recognized for decades. Moroff andBass (115) used the same test subjects in two experimental trials (90 mintreadmill exercise, 490C, 1.58 mls), once after preingestion of 2000 ml waterand once without preingestion. They reported (115) that hyperhydrationresulted in lower Tre, heart rate, and increased sweat secretion duringexercise-in the heat. Much later, Fortney et al. (56) studied the effects ofhypovolemia (diuretic-induced) and hypervolemia (albumin infusion) on bloodvolume and sweating responses. They observed that hypovolemia (8.7% decreasein blood volume) and hypervolemia (7.9% elevation in blood volume) effected 20min sweat rates of 270 ml and 541 ml, respectively (56), and hypothesized thatthe exacerbated release of PVP during hypovolemia may have contributed to thisdecrement. Earlier, Horstman and Horvath (91) reported that whole body,thigh, and abdomen sweat rates were significantly greater during euhydrationthan 3.6% hypohydration. Alternatively, Myhre and Robinson (116) used passiveheat exposure (50oC) to reduce PY by 7.8% (no fluid replacement) or 2.9% (NaClreplacement) and demonstrated no effects on sweat rates; In these experimentsthe PY differential may have been insufficient to elicit observabledifferences (87). In a related experiment Shannon et al. (154) exercised menin a cool (1SOC) environment, once after a subcutaneous administration of VPand a second time when subjects ingested 2% of their body weight in waterafter VP injection. Thirty through 60 min after the initiation of exercise,PY loss was reduced in the hyperhydrated group indicating the importanteffects of hydration level even when exogenous VP is administered (154). L

The mechanisms responsible for the increased PV of heat acclimation havebeen extensively investigated in recent years. Thus, Senay and co-investigators (152) exercised trained individuals (4 h/d, 40-50% V02 max, 3 dat 250C and lOd at 450C), and reported that between d 1 and d 2 of exercise inthe heat total plasma protein was elevated by 11.6% and PY increased by 9%.Further, during acclimation more protein and fluid were retained within thecirculatory system (152). Earlier, Senay (145) had compared the effects ofstair-stepping in a cool environment (200C) with the same exercise in the heat(400C), and reported that following acclimation, exercise in the heat wasaccompanied by hemodilution and maintenance or increments in plasma protein.Conversely, before heat acclimation exercise at 400C was characterized byhemoconcentration and net protein losses (145) while exercise in the coolenvironment even before heat acclimation was accompanied by hemodilution.These results led Senay (145, 147) to hypothesize that permeability changes incutaneous capillaries and availability of translocatable protein werepartially responsibile for the increased PV of heat acclimation.

When Senay later (146) compared the effects of heat acclimation on block-stepping at 340C, he again found that with acclimation, hemodilution wasmaintained for 2 h. He further hypothesized (146) that hemodilution orhemoconcentration responses may be dependent upon initial plasma osmolalitiesand circulating VP levels with the degree of hemodilution inversely correlatedwith initial osmolality and VP concentration. Interestingly, the same group(150) asserted that heat intolerant individuals (n15) failed to hemodilute tothe same extent as a group of heat tolerant men (n-19) when matched for V02max, under similar ambient and work conditions. Moreover, reduced aerobicexercise in the heat or deacclimation was accompanied by a decrement in plasmavolume mostly accounted for by significant reductions in total plasma protein(126). Even in rats, Horowitz and Samueloff (90) reported that dehydrationfollowing acclimation to 340C ambient was characterized by decreased efflux ofalbumin while colloid osmotic pressure and total protein mass increased.Studying desert-originated mice, they demonstrated (89) that dehydrationelicited no changes in plasma volume and a significant decrement in efflux ofalbumin from the circulatory system.

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FUTURE STUDIES 1

It Is noteworthy that In most of these studies addressingintercompartmental fluid shifts in acclimated, non-acclimated, heat tolerantand heat intolerant test subjects, potential endocrinological effectors havenot been investigated. In fact, while a wide variety of physiological,pharmacological, and physical factors have been identified as predisposing anIndividual to heat/exercise injury (155), we are unaware of any studies whichhave evaluated the association between these factors and endocrinological 6adaptations to exercise in the heat.

For example, we have recently compared the physiological and hematologicalresponses of older and younger men during 10 d of heat acclimation (124).While endocrinological responses are still being evaluated, the results ofthis study indicated no impairment of thermoregulatory responses when testsubjects were separated by 25 years in age, but matched for VO2 max andselected morphological factors. Alternatively, when Paolone et al. (125)compared the responses of young (26 y) and older (58 y) men to exercise in theheat, they observed that PRA was generally more markedly increased in theyounger group. They further concluded (125) that increased PRA in the youngerpopulation may have contributed to their increased ability to protect PVduring the first 60 min of exercise in the heat.

Additional studies on the role of endocrinological responses in the fluidshifts of heat acclimation, heat intolerance, and factors which predispose toheat injury may be useful in the design of pharmacological interventions toreduce the physiological strain of exercise in the heat. For example,although atrial hormone has been shown to counteract the vasoconstrictiveeffects of PRA and the anti-natriuretic effects of PA (111), to our knowledgeno studies have been conducted assessing its response during heat exposure orexercise in the heat. We have demonstrated in a small animal model thatduring moderate (10%) hypohydration PV is protected by an influx of water fromthe interstitial fluid compartment, and at 15% hypohydration, both theinterstitial and the intracellular compartment contribute to the maintenanceof PV (42). However, no studies of hormonal control, if existent, of theseintercompartmental shifts have been reported. In a much earlier study Giec(72) estimated the source of the water content of sweat during 2 h ofsedentary heat (50oC) exposure and concluded that 66% originated in theinterstitial fluid, 18% in the PV, and 16% in the erythrocytes and othercells.

Yet another understudied area is the complex series of endocrinologicalresponses occurring in females during exercise in the heat with respect tocircadian periodicity and phase of the menstrual cycle (88,158); for example, 9Horvath and Drinkwater (92) have reported a greater decrement in PV followingexercise in the heat during the luteal phase of the cycle. Grucza et al. (78)have observed several significant differences in sweating responses to heatexposure between men and women yet to our knowledge no studies have beenexecuted to investigate the endocrine correlates, if extant, of thesedifferences with respect to either the mcithly cycle or aging.

CONCLUSION

In this review we have attempted to address comprehensively the hormonaladaptations and responses which function in the maintenance of fluid andelectrolyte homeostasis during heat/exercise stress. Inconsistencies areapparent, but even more obvious are the myriad of experimental parameterswhich can affect experimental results. The exercise or, indeed, the heat mayrange from mild to severe, the time of exposure from acute to chronic, the 4

fitness status of the subjects from poor to elite - clearly, all these canaffect qualitatively and quantitatively adaptational profiles and response I

III|.|II |*|IIII II|1 -E i -m *gs- 'I.

patterns. Add to these the variables that can be more subtle or difficult toassess - hydration status, acclimation level, prior dietary history, and it isnot difficult to envision persistent inconsistencies or even apparentcontradictions. However, frequently, a close reading of the methodology willreveal logical and valid reasons for what at first glance appear to becontradictory reports. In fact, in reviewing the literature over the past 40years, one of the several striking differences to be noted is the morecomprehensive and complete descriptions of the test scenarios, experimentalconditions, test subjects, and methodologies that are currently provided. It bIs incumbent upon all investigators to maintain and expand this careful Cattention to experimental and methodological details so that data can beproperly evaluated.

It would have been useful, if it were possible, to correlate plasmahormonal response patterns and Intensities to fundamental physiologicalvariables relevant to exercise/heat stress. Information on indices related tophysiological strain (e.g. rectal temperature, heart rate, osmolality, sodium

* levels, plasma volume as estimated from hematocrit-hemoglobin changes) mayhave permitted comparisons of the endocrine response patterns with thesephysiological variables across experiments. For example, the endocrinological

* responses to sedentary (e.g. 1 h, 600C, euhydrated) heat exposure or exercise(e.g. 15 min 300C, 3% hypohydrated, 50% VO2max) in the heat provide useful,but independent, information on human adaptations to exercise/heat stress. Ifin these two experiments, however, the response patterns could be related tocommon physiological criteria as indicated above, then much more comprehensiveand useful interpretations could be made. For example, the intensity of thehormonal responses could be related to the physiological criteria affectingthis intensity in both experiments. Conclusions might be drawn as to hormonalresponses which contribute to the successful completion of either exercise orthe heat stress in both experiments, and the role of baroreceptors,osmoreceptors, volume receptors and thermoreceptors could be assessed. Thedegree of stress would be related to a physiological rather then anenvironmental/exercise criterion, and the diversity of environmental/exercisecriteria could be more comparable.

In closing, we would like to reemphasize that despite progress inunderstanding the role of hormonal action in regulating fluid and electrolytebalance during heat exposure/exercise In the heat, much remains unknown. Arecent brief review by McDougall (114) underscores this. In this succinctreport McDougall (114) discusses the factors which are instrumental to thecontrol of aldosterone secretion. He notes that this hormone is secreted onlyby cells of the zona alomerulosa of the adrenal cortex. Further,. he reportsthat angiotensin-T, adrenocort1cotropIc hormone, potassium loading, andsodium deprivation are all stimulatory to aldosterone secretion while atrialnatriurttic peptide is inhibitory. Despite these well-established regulatoryfactors, McDougall (114) asserts that several hypotheses and observationsregarding the control of aldosterone biosynthesis remain unconfirmed andsometimes confusing: the role of monoamines and other hormones, alterationsin adrenal sensitivity, occasional dissociation of the responses ofangiotensin 11 and aldosterone, central stimulation of aldosterone secretion.McDougall concludes that much further in vitro and in vivo work is necessaryNfor full understanding of the physiological control of aldosteronesecretionN. More generally, we also conclude that much further work isnecessary for a complete understanding of the role of the endocrine system inmaintaining fluid and electrolyte homeostasis during the challenge of heatexposure/exercise in the heat.

The authors express their sincere appreciation to Mrs. Susan E.P. Henryand Mrs. Diane Danielski for their outstanding word processing support.

The views of the authors do not purport to reflect the positions of theDepartment of the Army or the Department of Defense.

Citations of comercial organizations and trade names in this report donot constitute an officital Department of the Army endorsement or approval ofthe products or services of these organizations.

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