October-December 1981Ind. J. Phvsiol, Pharmae

ilg (Ed) RA Boakes and M.S.

d Book of Physiology, Sec. 6,ngton. D.C.• 1967.te fibers in the chorda tympani

f ratswith hypothalamic lesions.

ulation. Science, 135 : 375-

ts. J. Comp, Physiol. Psycho I••

Isin the control of food intake.

imentaryCanal. Vol. I. (Ed) C.F.

itumdu rat blanc. J. Pbvsiot;

In ; Food lntske and ChemicalSocieties Press. 1977.e mouse: Production. descrip-

n of food and water balance ;03, 1969.zing role on metabolism. In;. New York, 1977.

Intake and Chemical Senses,ress, 1977.970.

.. 166 : 17-30 1976.ard centres. Am_ J. Pbvsiot,

42.1973.activities of the ventromedial

x and the lateral hypothalamus.sraju. Elsevier Scientific Publi-

I. Behev, 7 : 385-394, 1971.take of rats. Ind. J. Physiol.

tivities of hypothalamic feeding

hedonic matrix; Relevance ofand Differentiation (eds.) E.

of the classically conditioneddorsal hippocampal ablation.

• ingestion of mea I. Physiol.

I to ventromedial nucleus and

In ; Hand Book of SensoryNew York. 1971.

ADRENERGIC RECEPTORS IN THE HYPOTHALAMUS CONCERNED WITHCONTROL OF ARTERIAL BLOOD PRESSURE: ELICITED BY ELECTRICAL

AND CHEMICAL STIMULATION

S. PURl. A. S. CHAKRABARTY AND S. K. LAL

Department of Physiology.

Maulana Azad Medical Colleqe & Associated Lok Nayak J.P. and G.B. Pant Hospitals.New De/hi - 110 002

(Received on October 10, 1980)

Summary: The study was made with the help of a chemitrode placed in various areas of thehypothalamus by the stereotaxic technique. for electrical and chemical stimulation (noradrenalineor isoprenaline) before and after microinjection of respective blockers (phenoxybenzamine orpractalol). The results indicated the presence of both alpha and beta-edrenoreceptors in theanterior and dorsomedial hypothalamus producing a depressor response, and. the presence ofalpha adrenoreceptors in the posterior and lateral hypothalamus producing a pressor response.

Key words : blood pressureisoprenaline

hypothalamic adrenergic receptorsnon -adrenaline

INTRODUCTION

Role of h'lpothalamus in the modulation of arterial blood pressure is well known(8, 9). Results of intraventricular and intrahypothalamic injection studies have suggestedthat central adrenoceptc rs are intimately concerned with control of arterial blood pressure.While intraventricular injection shows that both alpha receptors (1.2.3,4.10."') and betareceptors (1,3.13) are hypotensive, intrahypothalamic injection gives the opposite results(5, 6, 7). The present study was undertaken in order to elucidate the role of the hvpotha-larnic adrenoreceptors in tne control of blood pressure.

MATERIALS AND METHODS

Experiments were conducted in 23 cats of either sex, weighing between 2.5-4.0 kg, anaesthetised with intravenous choloralose (60 - 70 mg/kg). Chernitrodes.constructed from 24 gauge hypodermic needle. were implanted stereotaxically in the variousareas of the hypothalamus according to the coordinates as per Snider and Niemer (12).

320 Puri et al. October-December 1981Ind. J. Physiol. Pharmac.

Blood pressure with a pressure transducer (Polyrite-INCO) was recorded. Monopolarelectrical stimulation (4.V, 1 msec and 60 cycles/sec) was given at the tip ofchemitrode. Steel capillary (32 guage) was introduced through the needle. Hamiltonmicrosyringe connected to this fine steel capillary through a polythene tubing was usedfor microinjection 1.01ILI of either saline or drug was injected at a time. All the controlrecords were obtained after injection of 1.01ILI of saline and the effect of electrical stimu-lation of the hvpothalarnus was studied before and after microinjection of phenoxy-benza-mine (201pg) /practalol (201pg). Chemical stimulation of the hypothalamus with nor-adrenaline (10IILg)/isoprenaline (10IILg) was carried out before and after micro injection ofrespective blockers. Terminally the animals were killed and the brains perfused in situ with10% formalin. The site of stimulation and microinjection was confirmed by histologicaltechnique.

RESULTS

Pressor points treated with phenoxybenzamine after electrical stimulation (Fig. 1-A, B) :Eight locations in the lateral hypothalamus and four in the posterior hypothalamus

were studied. Following electrical stimulation, an increase in blood pressure was observedfrom both lateral and posterior hypothalamus. Pressor responses of all points except onein the lateral hypothalamus were affected by pretreatment with phenoxybenzamine.

Depressor points treated with phenoxybenzamine after electrical stimulation (Fig. 1-C,D):Three locations in the dorsornedial hypothalamus and two in the anterior hvpotha-

lamus were studied. Following electrical stimulation a decrease in blood pressure wasobserved. T'he depressor responses due to electrical stimulation of two points of thedorsomedial hypothalamus and one point of the anterior hvpothalarnus were blocked byphenoxybenzamine. However, phenoxybenzamine could not abolish the depressor effectdue to electrical stimulation of one point of the anterior and one point of the dorsomedialhypothalamus.

Depressor points treated with practalol after electrical stimulation (Fig. 1-£, F) :Three locations in the dorsomedial hypothalamus and .two in the anterior hypothala-

mus were studied. Depressor responses due to electrical stimulation of two points ofdorsomedial hypothalamus and one point of anterior hypothalamus ware blocked bypractalol. However, depressor responses due to electrical stiumulation of one each of thedorsomedial and anterior hypothalamus were not affected by pretreatment with eitherphenoxybenzamine or practalol.

Volume 25Number 4

Fig. 1

fOil

Electrical stimulation ofblockers. (phenoxyben(C) Dorsomedial hypothhypothalamus. Duration

October-December 1981Ind. J. Physiol. Pharmac.

recorded. Monopolargiven at the tip ofthe needle. Hamilton1enetubing was usedtime. All the controlset of electrical stimu-~nofphenoxy-benza-othalarnus with nor-after rnicroinjsctron of~perfusedin situ withnfirmedby histological

tion (Fig. l-A B) .'sterior hypothalamusressurewas observedall points except oneybenzamine.

ation(Fig.l-C,D).'the anterior hypotha-

blood pressure wasrf two points of the

us were blocked bythe depressor effect

t of the dorsomedial

. l-E,F) .'

e anterior hypothala-n of two points ofs ware blocked by

of one each of theatment with either

Volume 25Number 4

Hypothalamic Receptors and Arterial Blood Pressure 321

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Fig. 1 Electrical stimulation of various areas of the hypothalamus before and after microinjection of resp€ctiveblockers. (phenoxybenzarr,ine or practalof) : (A) Posterior hypothalamus, (B) Lateral hypothalamus,(C) Dorsornedial hypothalamus, (D) Anterior hypothalamus, (E) Anterior hypothalamus, (F) Dorsomedialhypothalamus. Duration of electrical stimulation (before and after the use of blockers) was 20 seconds.

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Fig. 2 Chemical stimulation (noradrenaline or isoprenaline) of various areas of the hypothalamus beforeand after microinjection of respective blockers : (A) Posterior hypothalamus (1.0 sec), (8) Lateralhypothalamus (0.5 sec), (C) Oorsomedial hvpothalamus (1.25 sec) (D) Anterior hypothalamus,(0.4 sec), (E) Oorsomedial hypothalamus (0.55 sec), (F) Anterior hypothalamus (0,25 sec). FiguresIn parenthesis indicate time-durations for the substance to produce respon se. This also includestime taken for the substance to pass through steel capillary and polythene tubing.

Volume 25Number 4

Effect of chemical stimulation cTwo locations each ir

rnus. in the posterior hypotline increased blood pressure(Fig, 3 - A C). On the contrdorsomedial hypothalamus deadrenaline was blocked by p~when injected in the anteriorwas blocked by practalol.

Fig. 3 Chemitrode and its PGA Post. hypothalam8 Ant. hypothalamC Lat. hypothalamuo Oorsomedialhyp

•

f the hypothalamus beforemus (1.0 sec). (B) Lateral(D) Anterior hypothalamusalamus(0.25 sec). Figuresonse. This also includestubing.

Hypothalamic Receptors and Arterial Blood Pressure 323Volume 25Number 4

Effect of chemical stimulation of the bvootheternus (Fig. 2) :Two locations each in the anterior hypothalamus, in the dorsomedial hvpothala-

rnus. in the posterior hypothalamus and four in the lateral hvpothalarnus. Noradrena-line increased blood pressure when injected in the lateral and posterior hypothalamus.(Fig. 3 - A C). On the contrary. noradrenaline when injected in the anterior and thedorsomedial hypothalamus decreased blood pressure (Fig. 3-6. D). The effect of nor-adrenaline was blocked by phenoxybenzamine. Isoprenaline also decreased blood pressurewhen injected in the anterior and dorsornedial hypothalamus. The effect of isoprenalinewas blocked by practalol.

Fig. 3: Chemitrode and its position in different areas of the hypothalamus.A Post. hypothalamus (A-B.5),B Ant. hypothalamus (A-13.5),C Lat. hypothalamus (A-9.5) andD Dorsomedial hypothalamus (A-9.5).

•

324 Puri et al. October- December 1981lnd , J. Phvsiol. Pharmac.

DISCUSSION

B( th electrical stimulation. before and after respective blockers and direct chemicalstimulation provide evidence that the posterior and the lateral hypothalamus contain alphaadrenoreceptors resulting in a pressor response while anterior and dorsornedial hypotha-lamus contain both alpha and beta adrenoreceptors producing a depressor response. Theresponses were blocked by intrahypothalamic microinjection of respective blockers. Thepresent study is more or less in line with the previous studies. Phillippu et at. (6)observed that the pressor response due to electrical stimulation of posterior hvpothalarnuswas blocked by alpha receptors inhibiting drugs such as tolazoline and piperoxan. Phi-IIippu and Schartner (7) also demonstrated the presence of alpha adrenoreceptors in theanterior hvpothalarnus producing a depressor response. Further studies (5) revealed thepresence of both alpha and beta receptors in the posterior hypothalamus producing thepressor response. The present investigation also indicates the presence of beta receptorsin the anterior and dorsomedial hvpothaiarnus mediating depressor response. This effectof beta receptor corresponds with the previous work following intraventricular injection(1.3.13). Thus the results of the present investigation suggest the presence of opposingmechanisms in the hvpothalarnus pressor or depressor receptors, controlling blood pre-ssure.

REFERENCES

1. Bhargava. K.P.• N. Misra and K.K. Tangri. An analysis of central adrenoceptors for control of cardicvascu'erfunction. Br. J. Pharmac •• 45 : 595-602. 1972.

2. Day. M.D. and AG. Roach. Central alpha and beta adrenoceptors modifying arterial blood pressure and heanrate in conscious cats. Br. J. Pharmac .• 51 : 325-333. 1974

3. Gagnon. D.J. and K.!. MelvilJe. Centrally mediated cardiovascular responses to isoprenaline. tm. J. Neuro-pharmac., 6 : 245-251. 1967.

4. McCubbin. J.W., Y. Kaneko and I.H. Page. Ability of serotonin and nor-epinephrine to mimic the central effectsof reserpine on vasomotor activity. Circulation Res., 8 : 849-858. 1960.

5. Philippu, A. and E. Kittel. Presence of beta-adrenoreceptors in the hypothalamus; their importance for the pressorresponse to hypothalamic stimulation. Naunyn-5chmiedeberg's Arch. Pharmac .• 297 : 219-225. 1977.

6. Philippu. A. W. Rosenberg and H. Przuntek, Effects of adrenergic drugs on pressor responses to hypothalamicstimulation. Naunyn-5chmiederberg's Arch. Pharmac., 278 : 373-386. 1973.

'1. Philippu. A. and P. Schartner. Inhibition by locally applied alpha-adrenoreceptor blocking drugs of the depressorresponse to stimulation of the anterior hypothalamus. Neunvn-Schmiedeberq's Arch. Phermec., 295 :1-7. 1976.

8. Pitts. R.F.• M.G. Larrabee and W.D. Bronts. An analysis of hypothalamic cardiovascular control. Am. J. Physiol .•134 : 359-383. 1941.

9. Ranson. S.E. and H.W. Magoun. The hypothalamus. Ergbn. Physio .• 41 : 55-163. 1939.10. Schmitt, H. Influence of adrenergic and cholinergic mechanisms on the centra! cardiovascular structures and

their interactions. In "Drugs and Central Synaptic Transmission" by Bradley P.B. and B.N. Dhawan. TheMacmillan Press Limited: p 63-88. 1976.

11. Share. N.N. and K.I. Melville. Centrally mediated sympathetic cardiovascular responses induced by intraventri-cular nor-epinephrine. J. Phermec. Exp. Ther., 141 : 15-21. 1963.

12. Snider, R.S. and W.T. Niemer. A. Stereotaxic atlas of the eat's brain. Chicago, Univ. of Chicago Press, 1961.13. Toda. N., Y. Matsuda and K. Shimamoto. Cardiovascular effects of sympathomimetic amines injected into the

cerebral ventricles of rabbits. Inr. J. Neurophermec., 8 : 451-461 1969.

FAI1.URE OF ACEEXPERIMENTA

Summary : Rats fed on acetthree weeks were subjectshydrochloride 8.5 mg/l 00g

Heart specimenswereAn equal number of rats wertreated rats were found topersistent oedema on the 12aspirin was seen on the fifth

Key words: myocardi

Ischaemic heart diseaicontemporary society. Treatpump failure. A different apdevelopment of myocardial neand thus reducing the size ofthis reduction of the extent 0

with less complications. RenoJol (16) has been tried; thtion. especially as a result oftrum of actions ascribed to(1-.9.25) inhibition of plate](1'7) and inhibition of neutroties. aspirin also reduces lipoacids (11) and causes increaof free fatty acids in plasma.in preventi ng coronary insufas coronary dilator (7). aspir

•