Mechanisms of the cardiovascular response to posterior hypothalamic nucleus administration of carbachol.
Unilateral microinjection of the cholinergic agonist carbachol (CCh) into the posterior hypothalamic nucleus (PHN) of conscious rats evoked a dose-dependent increase in mean arterial pressure (MAP). The pressor response was accompanied by tachycardia at all doses of CCh used (0.8-13.2 nmol), although the tachycardia was followed by a secondary bradycardia after the two highest doses (5.5 and 13.2 nmol). To determine the involvement of the autonomic nervous system and arginine vasopressin (AVP) in these cardiovascular changes, we administered selective receptor antagonists intravenously (i.v.) before microinjection of CCh into the PHN. The pressor response evoked by 3.3 nmol CCh could be attenuated by prazosin (an alpha 1-adrenoceptor blocker) or yohimbine (an alpha 2-adrenoceptor blocker) and completely blocked by the combination of prazosin and yohimbine. In contrast, the increase in MAP evoked by 5.5 and 13.2 nmol CCh could be attenuated by prazosin, yohimbine, or D[(CH2)5Tyr(Me)]AVP (AVPX, a V 1-vasopressin receptor blocker), and completely blocked by the combination of prazosin and AVPX. The tachycardia evoked by the 3.3-, 5.5-, and 13.2-nmol doses of CCh could be attenuated by propranolol (a beta-adrenoceptor blocker), and the secondary bradycardia evoked by 5.5 and 13.2 nmol CCh could be attenuated by either methylatropine (a muscarinic receptor blocker) or AVPX. These results suggest that administration of CCh into the PHN increases sympathetic nervous system activity, which increases MAP and heart rate (HR). The increase in MAP activates a baroreflex-mediated bradycardia by increasing vagal tone. This bradycardia is potentiated by an increase in circulating levels of AVP, which also contributes to the increased blood pressure (BP).
Martin
J R
JR
Department of Pharmacology, Kirksville College of Osteopathic Medicine, MO 63501, USA.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001286:Atropine Derivatives / Q000494:pharmacology; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D007034:Hypothalamus, Posterior / Q000187:drug effects* / Q000502:physiology; D007276:Injections, Intraventricular; D010276:Parasympatholytics / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000319:Adrenergic beta-Antagonists; D001286:Atropine Derivatives; D018679:Cholinergic Agonists; D010276:Parasympatholytics; C006649:methylatropine; D002217:Carbachol; D011433:Propranolol