Mechanoelastic Properties of the Aorta inChronically Hypertensive Conscious Rats

LlSETE C. MlCHELINI, P H . D . , AND EDUARDO M. KRIEGER, M.D.

SUMMARY The relationship between aortic caliber (AC) and aortic pressure (AP) was studied in elevennormotensive (NCR) and 17 one-kidney, one clip chronic renal hypertensive conscious Wistar rats (RHR) atrest and when transient changes in blood pressure were produced. The mean values for AC, AP, and tangentialstress were 20%, 75%, and 73% higher in RHR than NCR. Similarly, the aorta thickness was 21% greater butradius/thickness was unchanged. Pulse pressure increased by 51%, and aortic pulsation was twice that ofNCR. At control pressure, dynamic as well as mean distensibility of the aorta tended to be greater in RHR,but not statistically different. During transient changes in pressure, —40 to +40 mm Hg from control levels,dynamic distensibility was the same for both groups, but, at hypotensive levels, mean distensibility decreasedsignificantly in NCR. Mean distensibility was related to distending pressure; an overlap of NCR and RHRvalues occurred between 130 and 160 mm Hg. At the pressures studied, the dynamic strain of RHR wasmarkedly elevated because aortic pulsation (142%) increased more than caliber (20%). In spite of this, meanstrain was similar for both groups. Therefore, RHR responded to a pressure change with a greater change inmean caliber which was proportional to their larger control caliber. Alterations in pressure caused greaterchanges in the absolute values of diastolic caliber than pulsation for both groups. These properties of the aorticwall appear to be important for baroreceptor resetting in hypertension.(Hypertension 3 (suppl II): II-177-II-182, 1981)

KEYWORDS • stress • strain • distensibility • stiffness • aortic caliber •wall thickness • electrolytic transducer • baroreceptor resetting • hypertension

I T is well established that baroreceptors are resetto operate at the higher pressure level duringhypertension.1 Resetting lags behind the in-

crease in pressure and requires 1-2 days for comple-tion in the rat.2 It has not yet been established whetherresetting is due to changes in mechanical properties ofthe arterial wall or to changes in the receptors them-selves.' Alterations of the viscoelastic properties of thearterial wall can change the strain of the vessel and thedeformation of the baroreceptors. Therefore, resettingin hypertension has been attributed to reduced disten-sibility,4"" and thus stiffness of the arterial wall isgenerally considered to be increased.7'' However,decreased stiffness has also been reported for vesselsof DOCA- and renal-hypertensive rats.7'" At controlpressure, renal-hypertensive rabbits exhibited normaldistensibility.4 Studies on spontaneously hypertensiverats10 have not demonstrated changes in wall disten-sibility but have emphasized the role of uncoupling the

From the Department of Physiology, Faculty of Medicine ofRibeirSo Preto, SSo Paulo, Brazil

Supported by FAPESP (FundacSo de Amparo a Pesquisa doEstado de Sa"o Paulo) and FINEP (Financiadora de Estudos e Pro-jetos)

Address for reprints' Dr Lisete C Michehni, Department ofPhysiology, Faculty of Medicine of Ribeirao Preto, 14 100 RibeirSoPreto, Sao Paulo, Brazil.

receptors from the vessel wall and/or changes in thesensitivity of the baroreceptors themselves in account-ing for the resetting. The recent development of a newelectrolytic strain gauge11' " for the continuous meas-urement of aortic caliber in unanesthetized animalspermitted us to compare the properties of the aorta innormotensive and renal hypertensive rats underphysiological conditions.

Methods

Male Wistar normotensive (NCR, n = 11) andchronic (1-2 months) one-kidney, one clip hyper-tensive rats (RHR, n = 17) of similar age andweighing 200-250 g were studied.

Aortic caliber was measured with an electrolyticstrain gauge implanted into the first portion of thethoracic descending aorta 4 days before the experi-ment. Details of the construction and calibration ofthe transducer, as well as the surgical procedures forimplantation, have been given.11'" Aortic bloodpressure was recorded with a plastic cannula (PE 10connected to PE 50) inserted through the left carotidartery 1 day before. Systolic/diastolic and meanvalues for aortic caliber and pressure of conscious un-restrained rats were recorded simultaneously on aHewlett-Packard recorder (7848A) during the resting

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11-178 PROCEEDINGS/INTERAMERICAN SOCIETY SUPP II, HYPERTENSION, VOL 3, No 6, N O V / D E C , 1981

state and during transient alterations in bloodpressure. Pressure changes were produced by theremoval and infusion of blood from the femoral arteryor by intravenous bolus injection (femoral vein) ofnorepinephrine, acetylcholine, and sodium nitro-prusside. The doses of each pressor substance wereselected to produce a 10 to 40 mm Hg change inpressure. Similar results were obtained when pressurewas changed by blood or vasoactive substances. Thissimilarity was also reported by Pagani et al.11 instudies on sheep. At the end of the experiment, underether anesthesia, the aorta was fixed by perfusion witha modified Schlessinger solution to avoid retraction,and the thickness of the vessel wall (5) was deter-mined by morphometry.

The behavior of the aortic wall and its mechano-elastic properties were determined by correlatingpressure with caliber and using these data to calculatestress (a), strain (i), distensibility (calculated fromEp), and stiffness (Einc). For these calculations' theaortic wall was assumed to be a homogeneous elasticmedium, having isotrophy and incompressibility, witha Poisson ratio of 0.5. The parameters referring to thetangential direction were calculated by the followingformulas:'' '• w

A C AP X C

A C

Einc =X C

XO.75,AC

where P is the mean pressure, r is the mean radius, ACis the displacement of mean caliber (C) during a meanpressure change (AP). The present measurements ofpressure and caliber also permitted us to calculate theelastic properties of the aorta during the cardiac cycle,i.e., dynamic stress (<xdyn), strain (tdyn). distensibility(Epdyn), and stiffness (Eincdyn). The formulasemployed were the same, but instead of using thechanges in mean caliber and pressure, pulsatile valueswere used for each pressure level. As proposed byPeterson et al.' for arteries in vivo, we used the"pressure elastic modulus" (Ep) as the operationalmeasure of vessel stiffness, i.e., the reciprocal of dis-tensibility.

Results are reported as means ± SEM. Thestatistical significance of differences between groupsor within one group was analyzed by the unpaired andpaired t tests (p < 0.05).

Results

Control Measurement

Figure 1 illustrates simultaneous recordings of in-traaortic pressure and aortic caliber performed inconscious unrestrained NCR and RHR for periodsranging from 45 to 60 minutes. There was excellentagreement for both groups between the caliber andpressure curves, indicating that the electrolytic trans-ducer accurately measures the aortic caliber con-tinuously in awake animals, as documented pre-viously.11' ia

As shown in table 1, the mean arterial pressure ofRHR was 75% higher and the mean aortic caliber was20% greater than for NCR. The pulse pressure (AP)was 51% higher for RHR and the aortic pulsation(AC) was twice that observed for NCR. The thicknessof the aorta (5) was significantly increased (21%) inRHR, but the mean radius/wall thickness ratio (r/5)remained unchanged. There was no difference in heartrate in either group. The elastic properties of the aortaof NCR and RHR in the resting state are compared intable 1. The values for mean stress (a), dynamic stress(tfdyn). and dynamic strain (tdyn) were 73%, 49%, and97% higher for RHR than for NCR rats. When com-pared to NCR, the aorta of RHR exhibited a slightbut not significant increase in dynamic distensibility(Epdyn); the dynamic stiffness of the hypertensive wallwas slightly decreased but the values for RHR andNCR were not statistically different.

Transient Alterations in Blood Pressure

The behavior of the aortic caliber and the mechan-ical properties of the aorta were studied during tran-sient alterations in blood pressure. Arterial pressurewas changed from control values of 113 ± 3 mm Hgfor NCR and 178 ± 8 mm Hg for RHR in steps of 10mm Hg over the range - 4 0 to +40 mm Hg.

Figure 2 shows the alterations in mean aorticcaliber produced by changes in mean arterial pressure.The caliber was expressed as percent changes from thecontrol caliber for each animal, since there was greatvariability among individual values (6.019 to 7.221mm in NCR and 7.418 to 8.575 in RHR). The curvesrelating pressure to caliber were similar, except thatthose for RHR were shifted to the right. The valuesfor RHR were between 140 and 210 mm Hg, whilethose for NCR were in the 100-125 mm Hg range.The mean slope of the curves was 1.10 ± 0.24 and1.27 ± 0.09 X 10 ' mm/mm Hg for NCR and RHR,respectively, with high positive correlation coefficientsof 0.90 ± 0.02 and 0.93 ± 0.02. In the pressure rangeanalyzed, four RHR and two NCR curves exhibitedflattening at the highest distending pressure. All theother curves behaved as theoretically predicted for thepressure-caliber relationship of elastic arteries.

When blood pressure was altered ± 40 mm Hg inrelation to control values, the mean stress (fig. 3 D) in-creased progressively in both groups. The slopes of thecurves were identical, but RHR were shifted to highervalues (average increase of 56%). In spite of this, themean strain, which changed markedly with pressure,was the same for both groups (fig. 3 E). The meanstrain for RHR did not change because they exhibiteda larger response to pressure which was proportionalto their larger control caliber. Alterations in pressureproduced minor changes in mean RHR distensibility(fig. 3 F). The distensibility of NCR decreased sig-nificantly when blood pressure was reduced andshowed only a tendency (not statistically significant)to increase with pressure elevation. The aorta of RHRtended to be more distensible than that of NCR, butthe differences were not statistically significant except

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AORTIC DYNAMICS IN HYPERTENSION/AZ/cfce/im and Krieger 11-179

NORMOTENSIVE RENAL HYPERTENSIVE

FIGURE 1. Simultaneous recordings of pulsatile and mean aortic blood pressure (top) and pulsatile andmean aortic caliber (bottom) in conscious normotensive and hypertensive rats at different recording speedsA schematic diagram demonstrating the positions in the aorta of the electrolytic strain gauge and the arterialcannula is shown at the left

TABLE 1. Control Measurements in Conscious Unrestrained Normotensive Rats (NCR) and Renal Hyper-enswe Rats (RHR)

Aorta measurements

PressureAP (mm Hg)

Pulse pressureAP (mm Hg)

Heart rateHR (bpm)

CaliberAC (mm)

PulsationAC (mm)

Wall thickness

Radius/thicknessT/8

Wall stressa (X 10s dyne/cm2)

Dynamic stressairn (X 106 dyne/cm2)

Dynamic strain

Dynamic distensibilityEpdr, (X 10" dyne/cm2)

Dynamic stiffnessEinCdyn (X 107 dyne/cm2)

NCR(n = l l)

128 ± 3/77 ± 3(101 ±3)

51 ±2

409 ±9

6 557 ± 0.128/6 533 ± 0.128(6 545 ± 0 128)

0.024 ± 0 001

84.01 ±2.00

12.51 ±0 51

169 ±0.10

0.85 ± 0.05

0.37 ± 0.02

19.12 ± 1.50

17 96 ± 1 60

RHR(n = 17)

217±7*/140±5*(177 ± 6)*

77 ±4*

412 ±12

7.889 ± 0 099*/7.832 ± 0.098*(7.859 ± 0.099)*

0 058 ± 0.006*

101 55 ± 2.51*

12.36 ± 0.33

2.92 ±0.12*

1.27 ±0.09*

0.73 ± 0.08*

16.08 ± 1 64

14.38 ± 1.52

*Significant (p < 0.05) when compared with control values.

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11-180 PROCEEDINGS/INTERAMERICAN SOCIETY SUPP II, HYPERTENSION, VOL 3, No 6, N O V / D E C , 1981

102r

crm 101_i<ooHcr< 100z<LJ

9 9 L

NCRRHR

50 100 150 200 250

MEAN ARTERIAL PRESSURE (mmHg)

FIGURE 2. Percentage changes of aortic caliber duringtransient alterations in arterial pressure in normotensive(NCR) and one-kidney, one clip chronic hypertensive rats(RHR). The horizontal dashed line represents the controlcaliber for each animal

in response to pressure reduction when mean disten-sibility decreased markedly in NCR. Figure 3 F alsoshows that the absolute distensibility values weresimilar when arterial pressure decreased in RHR andincreased in NCR. This fact is more clearly demon-strated in figure 4 left, which shows that the mean dis-tensibility values for both groups lie on the samecurve. In the 130-160 mm Hg range, the values forNCR and RHR overlap, but the left end of the curverefers only to the normotensive rats and the right endto the hypertensive rats. Similar results were obtainedwhen the elastic behavior of the aorta was assessed interms of mean stiffness (Einc). As seen in figure 4 rightfor both groups, aortic stiffness was greater the lowerthe tangential stress of the wall. The highest stiffnessvalue was found when arterial pressure was reduced inNCR. The lowest stiffness was observed in response toa 40 mm Hg transient increase in pressure in RHR.

The pulsatile behavior of the aorta is illustrated infigure 3 A, B, and C. Whereas pulsatile stress in-creases with pressure elevation in RHR, it remainsalmost stable in NCR, except for 40 mm Hg hyper-tension, where dynamic stress was significantly in-creased. For the entire range from —40 to +40 mmHg, the dynamic stress for RHR was on the average99% higher than for NCR. Again, the pulsatile strainof the aorta (fig. 3 B) was greater than for NCR: atcontrol pressure, the dynamic strain was twice thatobserved for NCR. When the pressure was increasedabove the control level, the pulsatile strain also in-

creased and at +40 mm Hg was significantly elevatedby 22% and 36% for RHR and NCR, respectively.The opposite was observed when the pressure wasreduced: at —40 mm Hg there was a significantdecrease of 25% (RHR) and 14% (NCR). When aorticpulsation was related to distending pulse pressure (fig.3 C), the dynamic distensibility tended to be greaterfor RHR than NCR, but the differences were notstatistically significant. For both groups, dynamic dis-tensibility had a tendency to decrease when pressurefell. There was no significant difference between thegroups in terms of dynamic stiffness (data not shown).

The data presented in figure 3 B and E, expressed aspercentages, show that changes in mean caliber aregreater than changes in pulsation, suggesting thatalterations in diastolic caliber were the most impor-tant single factor. This can be demonstrated une-quivocally by considering the absolute values for aor-tic caliber. In response to an increase in pressure of 40mm Hg, the systolic caliber of NCR and RHR in-creased 0.047 and 0.066 mm. The increase in diastoliccaliber, 0.038 mm (NCR) and 0.053 mm (RHR), ac-counted for 81% and 80% of the total differences insystolic caliber. The pulsation increased by only 19%(0.009 mm) and 20% (0.013 mm) for NCR and RHR,respectively.

Discussion

The electrolytic strain gauge implanted in theanimals to record the systolic, diastolic, and meancalibers permitted the analysis of the dynamic (pul-satile) as well as the mean values for stress, strain, dis-tensibility, and stiffness of the aorta in awake rats.The data reported here show for the first time that un-der physiological conditions the pulsation of the aortaof the renal hypertensive rat was twice that of the nor-motensive rat in spite of the fact that distensibility andstiffness were similar.

In hypertensive rats, both the caliber and thicknessof the aortic wall increased in the same proportion;therefore, the radius/thickness ratio was unchanged.Thus, the tangential wall stress increased only becauseof pressure elevation. The dynamic strain wasmarkedly elevated in hypertension because the in-crease in aortic pulsation (142%) was much greaterthan the increase in caliber (20%). An interesting find-ing is that during transient changes in pressure theratio of change of displacement of mean caliber/con-trol caliber (mean strain) was similar in hypertensiveand normotensive rats, suggesting the same "oper-ating level" for both groups. Moreover, dynamic andmean distensibility were not different at resting con-ditions. This last result is in agreement with data re-ported for mean distensibility in renal hypertensiverabbits4 and in spontaneously hypertensive rats.10

In the experiments reported here on conscious rats,the changes in pressure were ±40 mm Hg, and there-fore extreme changes in pressure like those obtained invitro were not produced. This may explain why only2/7 NCR and 4/9 RHR showed the decrease in dis-tensibility with increasing transmural pressure which

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AORTIC DYNAMICS IN HYPERTENSION/A/icA<?//n/ and Krieger

B »• C

11-181

-40 -20 C +20 +40 -40 -20 C

TRANSIENT CHANGES IN MEAN+20 +40

ARTERIAL

-40 -20 C

PRESSURE (mmHg)+20 +40

FIGURE 3. Dynamic (top) and mean (bottom) mechanoelastic properties of the aorta during transientchanges in pressure (—40 to +40 mm Hg). A and D = stress; B and E = strain; C and F = distensibility.Symbols represent means, and vertical bars ± SE * = significant difference (p < 0.05) between RHR andNCR, f = value significantly different (p < 0.05) from the control.

is usually reported in the literature." Increase in dis-tensibility with pressure, observed in the majority ofour experiments, has also been reported for dogs,18

cats," rabbits,4 and man17 when the changes inpressure were not extreme.

The displacement of the baroreceptor firing rangeto a new level lasts 1-2 days, whenever there is a per-manent change in pressure in either direction, hyper-tension or hypotension.1'18 The baroreceptors inchronic renal hypertensive rats discharge in ap-parently normal fashion1'' M even though, as shownhere, the aortic pulsation of these rats was twice thenormal value. It is interesting to speculate that baro-receptors are also part of the adaptative changes in theaortic wall produced by hypertension and, therefore,in the new state of equilibrium achieved by the aorticwall (coincidentally, the aorta takes 1-2 days to dilateduring acute hypertension — Michelini, L. C. andKrieger, E. M., unpublished results) the baroreceptorsare normally activated even when the pulsation isgreater. In this new resting position, the increase in fir-ing produced by transient pressure elevation is deter-mined mainly by stretching the diastolic caliber. Thisinterpretation derives from another important finding

in the present study, i.e., during transient alterationsin pressure the major determinant for baroreceptordistortion was shown to be the displacement ofdiastolic caliber rather than vessel pulsation for bothgroups. The fact that the percentage of changes indiastolic caliber in relation to the control was the samefor normotensive and hypertensive rats reinforces the

= £ 10

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Z

16L 1

'/

UJ "

Mil

1 0 ;

100 150 200MEAN ARTERIAL PRESSURE

(mmHg)

1 2 3 4TANGENTIAL STRESS

U106 dyne/cm2)

FIGURE 4. Alterations in mean distensibility (left,) andmean stiffness (right,) of the aorta in NCR ( • ) and RHR(o). Symbols represent means and vertical bars ± SE.

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11-182 PROCEEDINGS/INTERAMERICAN SOCIETY SUPP II, HYPERTENSION, VOL 3, No 6, NOV/DEC, 1981

idea that adaptative mechanisms in the aorta compen-sate for the concurrent geometrical changes to main-tain a nearly constant level of distensibility. This inter-pretation has been made by Pagani et al.18 to explainthe same distensibility exhibited at baseline levels ofaortic stress by adult and newborn sheep, althoughthere are great differences in vessel wall geometry.

It is difficult to compare the present results withmany others reported in the literature because ofmarked differences in species, techniques, experi-mental design, and method of calculation of arterialelasticity. The mean values for distensibility andstiffness reported here are greater than those describedby Cox7 for rat carotid segments but similar to thosereported by Berry and Greenwald' for rat aorta in situwhen the later values of Einc in SI units (X10* N/mJ)are converted to CGS units (X107 dyne/cm1). Onepossible explanation for the apparently high stiffnessfound in the intact rat is the significant aortic muscletone.8 In fact, the aorta of the rat has several concen-tric muscular lamellae' and, as stressed by Dobrin,8

the smooth muscle layer plays an important role indetermining aortic stiffness in the physiologicalpressure range. Moreover, the aortic muscle of the ratseems to play an important role in maintaining theaortic caliber during the first few hours of acutehypertension.11

Acknowledgments

The authors thank Edson D Moreira for his excellent technicalassistance

References1 McCubbin JW, Ferrano CM' Baroreceptor reflexes and hyper-

tension In Hypertension, edited by Genest J, Koiw E, KuchelO New York- McGraw-Hill, 1977, p 128

2 Krieger EM Time course of baroreceptor resetting in acutehypertension Am J Physiol 218: 486, 1970

3 Pickering TG, Sleight P Baroreceptors and hypertension. InHypertension and Brain Mechanisms, edited by De Jong W,Provoost AP, Shapiro AP Amsterdam. Elsevier, 1977, p 43

4 Aars H Relationship between blood pressure and diameter ofascending aorta in normal and hypertensive rabbits. ActaPhysiol Scand 75: 397, 1969

5 Angell-James JE Characteristics of single aortic and right sub-clavian baroreceptor fiber activity in rabbits with chronic renalhypertension Circ Res 32: 149, 1973

6 Peterson LH, Jensen RE, Parnell J Mechanical properties ofarteries in vivo Circ Res 8: 622, 1960

7 Cox RH Carotid artery mechanics and composition in renaland DOCA hypertension in the rat. Cardiovasc Med 2: 761,1977

8 Dobrin PB Mechanical properties of arteries Physiol Rev 58:397, 1978

9 Berry CL, Greenwald SE' Effects of hypertension on the staticmechanical properties and chemical composition of the rat aor-ta Cardiovasc Res 10: 437, 1976

10 Brown AM Receptors under pressure An update on baro-receptors Circ Res 46: 1, 1980

11. Compagno LT, Leite JVP, Krieger EM Continuous measure-ment of aortic caliber in conscious rats Effect of acute hyper-tension Mayo Chn Proc 52: 433, 1977

12 Michelini LC, Leite JVP, Kneger EM A new electrolytic straingauge to study changes in aortic caliber produced by hyper-tension In Prophylactic Approach to Hypertensive Diseases,edited by Yamon Y, Lovenberg W, Freis ED New YorkRaven Press, 1979, p 249

13 Pagani M, Mirsky I, Baig H, Manders WT, Kerhof P, VatnerSF Effects of age on aortic pressure-diameter and elasticstiffness-stress relationship in unanesthetized sheep Circ Res44: 420, 1979

14 Bergel DH The static elastic properties of the arterial wall. JPhysiol 156: 445, 1961

15 Gow BS, Taylor MG' Measurement of visco-elastic propertiesof arteries in the living dog Circ Res 23: 111, 1968

16 Leitz KH, Arndt JO Die Durchmesser-Druck-Bezeilhung desIntakten GefBbgcbietes der A carotis communis von Katzen.PflOgers Arch 301: 50, 1968

17 Arndt JO, Klauske J, Mersch F The diameter of the intactcarotid artery in man and its change with pulse pressurePflugers Arch 301: 230, 1968

18 Salgado HC, Krieger EM. Time course of baroreceptor reset-ting in short-term hypotension in the rat Am J Physiol 234:H552, 1978

19 Krieger EM, Marseillan RF Neural control in experimentalhypertension The role of baroreceptor and splanchnic fibers.Acta Physiol Lat Am 16: 343, 1966

20 Salgado HC, Krieger EM. Reversibility of baroreceptor adap-tation in chronic hypertension Clin Sci Mol Med 45: 123s,1973

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L C Michelini and E M KriegerMechanoelastic properties of the aorta in chronically hypertensive conscious rats.

Print ISSN: 0194-911X. Online ISSN: 1524-4563 Copyright © 1981 American Heart Association, Inc. All rights reserved.

is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231Hypertension doi: 10.1161/01.HYP.3.6_Pt_2.II-177

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