ADRENERGIC RECEPTORS IN THE HYPOTHALAMUS CONCERNED WITH CONTROL OF ARTERIAL BLOOD PRESSURE: ELICITED BY ELECTRICAL AND CHEMICAL STIMULATION

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1 ADRENERGIC RECEPTORS IN THE HYPOTHALAMUS CONCERNED WITH CONTROL OF ARTERIAL BLOOD PRESSURE: ELICITED BY ELECTRICAL AND CHEMICAL STIMULATION S. PURl. A. S. CHAKRABARTY AND S. K. LAL Department o Physiology. Maulana Azad Medical Colleqe & Associated Lok Nayak J.P. and G.B. Pant Hospitals. New De/hi (Received on October ) Summary: The study was made with the help o a chemitrode placed in various areas o the hypothalamus by the stereotaxic technique. or electrical and chemical stimulation (noradrenaline or isoprenaline) beore and ater microinjection o respective blockers (phenoxybenzamine or practalol). The results indicated the presence o both alpha and beta-edrenoreceptors in the anterior and dorsomedial hypothalamus producing a depressor response and. the presence o alpha adrenoreceptors in the posterior and lateral hypothalamus producing a pressor response. Key words : blood pressure isoprenaline hypothalamic adrenergic receptors non -adrenaline INTRODUCTION Role o h'lpothalamus in the modulation o arterial blood pressure is well known (8 9). Results o intraventricular and intrahypothalamic injection studies have suggested that central adrenoceptc rs are intimately concerned with control o arterial blood pressure. While intraventricular injection shows that both alpha receptors ( "') and beta receptors (13.13) are hypotensive intrahypothalamic injection gives the opposite results (5 6 7). The present study was undertaken in order to elucidate the role o the hvpothalarnic adrenoreceptors in tne control o blood pressure. MATERIALS AND METHODS Experiments were conducted in 23 cats o either sex weighing between kg anaesthetised with intravenous choloralose (60-70 mg/kg). Chernitrodes. constructed rom 24 gauge hypodermic needle. were implanted stereotaxically in the various areas o the hypothalamus according to the coordinates as per Snider and Niemer (12).

2 320 Puri et al. October-December 1981 Ind. J. Physiol. Pharmac. Blood pressure with a pressure transducer (Polyrite-INCO) was recorded. Monopolar electrical stimulation (4.V 1 msec and 60 cycles/sec) was given at the tip o chemitrode. Steel capillary (32 guage) was introduced through the needle. Hamilton microsyringe connected to this ine steel capillary through a polythene tubing was used or microinjection 1.01ILI o either saline or drug was injected at a time. All the control records were obtained ater injection o 1.01ILI o saline and the eect o electrical stimulation o the hvpothalarnus was studied beore and ater microinjection o phenoxy-benzamine (201pg) /practalol (201 pg). Chemical stimulation o the hypothalamus with noradrenaline (10IILg)/isoprenaline (10IILg) was carried out beore and ater micro injection o respective blockers. Terminally the animals were killed and the brains perused in situ with 10% ormalin. The site o stimulation and microinjection was conirmed by histological technique. RESULTS Pressor points treated with phenoxybenzamine ater electrical stimulation (Fig. 1-A B) : Eight locations in the lateral hypothalamus and our in the posterior hypothalamus were studied. Following electrical stimulation an increase in blood pressure was observed rom both lateral and posterior hypothalamus. Pressor responses o all points except one in the lateral hypothalamus were aected by pretreatment with phenoxybenzamine. Depressor points treated with phenoxybenzamine ater electrical stimulation (Fig. 1-CD): Three locations in the dorsornedial hypothalamus and two in the anterior hvpothalamus were studied. Following electrical stimulation a decrease in blood pressure was observed. T'he depressor responses due to electrical stimulation o two points o the dorsomedial hypothalamus and one point o the anterior hvpothalarnus were blocked by phenoxybenzamine. However phenoxybenzamine could not abolish the depressor eect due to electrical stimulation o one point o the anterior and one point o the dorsomedial hypothalamus. Depressor points treated with practalol ater electrical stimulation (Fig. 1- F) : Three locations in the dorsomedial hypothalamus and.two in the anterior hypothalamus were studied. Depressor responses due to electrical stimulation o two points o dorsomedial hypothalamus and one point o anterior hypothalamus ware blocked by practalol. However depressor responses due to electrical stiumulation o one each o the dorsomedial and anterior hypothalamus were not aected by pretreatment with either phenoxybenzamine or practalol.

3 Volume 25 Number 4 Hypothalamic Receptors and Arterial Blood Pressure 321 TIV _ I+J "":t:--+++-'-...-~.----'"t' \ _. P.- sin ~. W'P I TIME MARKER " i-tl-+I'I"I Hlril+t ~ _ tr'm Ill: T'ME;MJlRK A t ST F Fig. 1 Electrical stimulation o various areas o the hypothalamus beore and ater microinjection o resp ctive blockers. (phenoxybenzarrine or practalo) : (A) Posterior hypothalamus (B) Lateral hypothalamus (C) Dorsornedial hypothalamus (D) Anterior hypothalamus (E) Anterior hypothalamus (F) Dorsomedial hypothalamus. Duration o electrical stimulation (beore and ater the use o blockers) was 20 seconds.

4 M. Volume 25 Number 4 A Eect o chemical stimulation c Two locations each ir rnus. in the posterior hypot line increased blood pressure (Fig 3 - A C). On the contr dorsomedial hypothalamus de adrenaline was blocked by p~ when injected in the anterior was blocked by practalol. T NOR ~O. " + NO. AOR; PHaI. ISOP"IN I$OPII:I:M NOII:AOI\ ' NOIlM)R. PHtN :roo! I~' E 4. lio NOR.ADI NOR.AO*. ~~~~.~.~ too tsov ISOPI N. PRAC. i " "... ISOPRVt Fig. 3 Fig. 2 Chemical stimulation (noradrenaline or isoprenaline) o various areas o the hypothalamus beore and ater microinjection o respective blockers : (A) Posterior hypothalamus (1.0 sec) (8) Lateral hypothalamus (0.5 sec) (C) Oorsomedial hvpothalamus (1.25 sec) (D) Anterior hypothalamus (0.4 sec) (E) Oorsomedial hypothalamus (0.55 sec) (F) Anterior hypothalamus (025 sec). Figures In parenthesis indicate time-durations or the substance to produce respon se. This also includes time taken or the substance to pass through steel capillary and polythene tubing. Chemitrode and its PG A 8 C o Post. hypothalam Ant. hypothalam Lat. hypothalamu Oorsomedial hyp

5 Hypothalamic Volume 25 Number 4 Receptors and Arterial Blood Pressure 323 Eect o chemical stimulation o the bvootheternus (Fig. 2) : Two locations each in the anterior hypothalamus in the dorsomedial hvpothalarnus. in the posterior hypothalamus and our in the lateral hvpothalarnus. Noradrenaline 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 the dorsomedial hypothalamus decreased blood pressure (Fig D). The eect o noradrenaline was blocked by phenoxybenzamine. when injected in the anterior and dorsornedial was blocked by practalol. Fig. 3: the hypothalamus beore mus (1.0 sec). (B) Lateral (D) Anterior hypothalamus alamus(0.25 sec). Figures onse. This also includes tubing. Isoprenaline also decreased blood pressure hypothalamus. The eect o isoprenaline Chemitrode and its position in dierent areas o the hypothalamus. A B C D Post. hypothalamus (A-B.5) Ant. hypothalamus (A-13.5) Lat. hypothalamus (A-9.5) and Dorsomedial hypothalamus (A-9.5).

6 324 Puri et al. October- December 1981 lnd J. Phvsiol. Pharmac. DISCUSSION B( th electrical stimulation. beore and ater respective blockers and direct chemical stimulation provide evidence that the posterior and the lateral hypothalamus contain alpha adrenoreceptors resulting in a pressor response while anterior and dorsornedial hypothalamus contain both alpha and beta adrenoreceptors producing a depressor response. The responses were blocked by intrahypothalamic microinjection o respective blockers. The present study is more or less in line with the previous studies. Phillippu et at. (6) observed that the pressor response due to electrical stimulation o posterior hvpothalarnus was blocked by alpha receptors inhibiting drugs such as tolazoline and piperoxan. Phi- IIippu and Schartner (7) also demonstrated the presence o alpha adrenoreceptors in the anterior hvpothalarnus producing a depressor response. Further studies (5) revealed the presence o both alpha and beta receptors in the posterior hypothalamus producing the pressor response. The present investigation also indicates the presence o beta receptors in the anterior and dorsomedial hvpothaiarnus mediating depressor response. This eect o beta receptor corresponds with the previous work ollowing intraventricular injection (1.3.13). Thus the results o the present investigation suggest the presence o opposing mechanisms in the hvpothalarnus pressor or depressor receptors controlling blood pressure. REFERENCES 1. Bhargava. K.P. N. Misra and K.K. Tangri. An analysis o central adrenoceptors or control o cardicvascu'er unction. Br. J. Pharmac 45 : Day. M.D. and AG. Roach. Central alpha and beta adrenoceptors modiying arterial blood pressure and hean rate in conscious cats. Br. J. Pharmac. 51 : Gagnon. D.J. and K.!. MelvilJe. Centrally mediated cardiovascular responses to isoprenaline. tm. J. Neuropharmac. 6 : McCubbin. J.W. Y. Kaneko and I.H. Page. Ability o serotonin and nor-epinephrine to mimic the central eects o reserpine on vasomotor activity. Circulation Res. 8 : Philippu A. and E. Kittel. Presence o beta-adrenoreceptors in the hypothalamus; their importance or the pressor response to hypothalamic stimulation. Naunyn-5chmiedeberg's Arch. Pharmac. 297 : Philippu. A. W. Rosenberg and H. Przuntek Eects o adrenergic drugs on pressor responses to hypothalamic stimulation. Naunyn-5chmiederberg's Arch. Pharmac. 278 : '1. Philippu. A. and P. Schartner. Inhibition by locally applied alpha-adrenoreceptor blocking drugs o the depressor response to stimulation o the anterior hypothalamus. Neunvn-Schmiedeberq's Arch. Phermec. 295 : Pitts. R.F. M.G. Larrabee and W.D. Bronts. An analysis o hypothalamic cardiovascular control. Am. J. Physiol. 134 : Ranson. S.E. and H.W. Magoun. The hypothalamus. Ergbn. Physio. 41 : Schmitt H. Inluence o 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. The Macmillan Press Limited: p Share. N.N. and K.I. Melville. Centrally mediated sympathetic cardiovascular responses induced by intraventricular nor-epinephrine. J. Phermec. Exp. Ther. 141 : Snider R.S. and W.T. Niemer. A. Stereotaxic atlas o the eat's brain. Chicago Univ. o Chicago Press Toda. N. Y. Matsuda and K. Shimamoto. Cardiovascular eects o sympathomimetic amines injected into the cerebral ventricles o rabbits. Inr. J. Neurophermec. 8 :