Interaction between renin-angiotensin system and cholinergic system in brain.
Intracerebroventricular (i.c.v.) injection of hemicholinium-3 (HC-3; 20 micrograms), which depletes acetylcholine stores in brain, reduced the increase in mean arterial pressure (MAP) and the drinking, but not the decrease in heart rate (HR), induced by intraventricular injection of angiotensin II (ANG II, 50 and 100 ng) in conscious rats. Intraventricular injection of atropine (up to 1 microgram) decreased only the pressor effect, while larger doses (up to 10 micrograms) decreased the bradycardia, too. Mecamylamine (100 micrograms i.c.v.) reduced the pressor response induced by angiotensin, without influencing the decrease in heart rate. A dose of 50 micrograms of mecamylamine had no effect. Neither atropine (10 micrograms i.c.v.) nor mecamylamine (50 micrograms i.c.v.) affected thirst induced by angiotensin. Intravenous (i.v.) atropine, but not atropine methylbromide, strongly reduced the drinking effect. The increase in arterial pressure and the decrease in heart rate induced by intraventricular injection of physostigmine, as well as the drinking behaviour after carbachol (250 ng, i.c.v.) or the increase in arterial pressure following intravenous injection of physostigmine (in methylatropine-pretreated rats), were not influenced by either saralasin (up to 10 micrograms/kg, i.c.v.) or captopril (up to 50 micrograms, i.c.v.). These results suggest that: (1) the increase in mean arterial pressure and drinking behaviour, induced by intraventricular injection of angiotensin II, are partially mediated via acetylcholine in brain, acting through muscarinic receptors; (2) decrease in heart rate induced by angiotensin II is not baroreceptor reflex-mediated; (3) the brain renin-angiotensin system does not participate in the cardiovascular and behavioural effect induced by cholinergic stimulation in the brain.