Modulatory effect of brain acetylcholine on reflex-induced bradycardia and tachycardia in conscious rats.

The effects of intracerebroventricular (i.c.v.) injection of physostigmine and hemicholinium-3 (HC-3) on reflex bradycardia and tachycardia have been studied in unanesthetized rats. The reflex increases and decreases in heart rate were elicited by i.v. injection of norepinephrine and sodium nitroprusside, respectively. Physostigmine (5-10 micrograms) increased basal mean arterial pressure (MAP), reduced basal heart rate (HR), enhanced the reflex bradycardia and reduced reflex tachycardia. Physostigmine did not modify either the pressor effect of norepinephrine, the depressor effect of sodium nitroprusside or the responsiveness of peripheral muscarinic receptors. Pretreatment (i.c.v.) with atropine (0.3 micrograms) completely abolished the effect of physostigmine on MAP, HR, reflex bradycardia and reflex tachycardia. Pretreatment (i.c.v.) with mecamylamine (50 micrograms) did not modify the effect of the cholinesterase inhibitor on MAP, HR and reflex tachycardia, but inverted its effect on reflex bradycardia. Injection of HC-3 (20 micrograms i.c.v.) did not modify MAP, but reduced HR and inhibited both reflex bradycardia and reflex tachycardia. The HC-3 bradycardic effect started within minutes and lasted for about 1 hr, while the depressor effect on the reflexes began only after 15 min and continued for several hours. In addition, i.c.v. pretreatment with HC-3 completely abolished all the effects of physostigmine on MAP, HR, reflex bradycardia and reflex tachycardia. These results suggest that brain acetylcholine has a modulatory effect on baroreceptor reflexes. This modulation operates through muscarinic receptors in reflex tachycardia and through both muscarinic and nicotinic receptors in reflex bradycardia.