MECHANISMS OF THE CARDIOVASCULAR-RESPONSE TO POSTERIOR HYPOTHALAMIC NUCLEUS ADMINISTRATION OF CARBACHOL

Unilateral microinjection of the cholinergic agonist carbachol (CCh) i nto the posterior hypothalamic nucleus (PHN) of conscious rats evoked a dose-dependent increase in mean arterial pressure (MAP). The presser response was accompanied by tachycardia at all doses of CCh used (0.8 -13.2 nmol), although the tachycardia was followed by a secondary brad ycardia after the two highest doses (5.5 and 13.2 nmol). To determine the involvement of the autonomic nervous system and arginine nine vaso pressin (AVP) in these cardiovascular changes, we administered selecti ve receptor antagonists intravenously (i.v.) before microinjection of CCh into the PHN. The presser response evoked by 3.3 nmol CCh could be attenuated by prazosin (an alpha(1)-adrenoceptor blocker) or yohimbin e (an alpha(2)-adrenoceptor blocker) and completely blocked by the com bination of prazosin and yohimbine. In contrast, the increase in MAP e voked by 5.5 and 13.2 nmol CCh could be attenuated by prazosin, yohimb ine, or D[(CH2)(5)Tyr(Me)]AVP (AVPX, a V-1-vasopressin receptor blocke r), and completely blocked by the combination of prazosin and AVPX. Th e tachycardia evoked by the 3.3-, 5.5-, and 13.2-nmol doses of CCh cou ld be attenuated by propranolol (a beta-adrenoceptor blocker), and the secondary bradycardia evoked by 5.5 and 13.2 nmol CCh could be attenu ated by either methylatropine (a muscarinic receptor blocker) or AVPX. These results suggest that administration of CCh into the PHN increas es sympathetic nervous system activity, which increases MAP and heart rate (HR). The increase in MAP activates a baroreflex-mediated bradyca rdia by increasing vagal tone. This bradycardia is potentiated by an i ncrease in circulating levels of AVP, which also contributes to the in creased blood pressure (BP).