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Increased central cholinergic activity in rat models of hypertension
Abstract:
The role of brain acetylcholine (ACh) in the development and maintenance of experimental hypertension was evaluated. Single, acute injections of hemicholinium-3 (HC-3), 20 micrograms, were made into the lateral cerebral ventricle of unanesthetized rats during development of hypertension in the spontaneously hypertensive rat (SHR) or following induction of deoxycorticosterone-salt (DOCA), aortic coarctation (AoCo), and Grollman hypertension. HC-3 caused nonsignificant reductions in blood pressure (BP) when injected in SHR and Wistar-Kyoto (WKY) controls at 5 and 8 weeks of age. At 12 weeks in SHR, depressor responsiveness increased concomitantly with the development of hypertension and reached maximal stable effect during established hypertension (18-60 weeks). Intravenous (i.v.) infusion of sodium nitroprusside (NaNP) normalized BP of adult SHR, yet did not prevent the hypotensive response to HC-3. In DOCA hypertension, the HC-3 hypotensive effect (1 week postinduction) preceded establishment of significantly elevated BP (3 weeks), but then remained constant despite a continual rise in BP (2-6 weeks). In the AoCo model, onset of severe hypertension (day 2 postinduction) preceded the appearance of significant depressor responsiveness to HC-3 (day 10). Although BP remained uniformly elevated from 10 to 40 days, the magnitude of the depressor response was stable between 10 and 28 days, then increased further at day 40. At the only time studied, 4 weeks after induction of hypertension, HC-3 also lowered BP of Grollman rats. Marked bradycardia occurred in all models and controls. The results suggest that enhancement of central cholinergic neurotransmission is a common feature of experimental hypertension regardless of its etiology. Increased brain cholinergic function appears to be involved in the development (but not the initiation) and maintenance of elevated BP in the SHR, whereas it may play a role in the initiation of DOCA hypertension and in the maintenance of AoCo hypertension.