Angiotensin AT1-receptor blockers enhance cardiac responses to parasympathetic nerve stimulation via presynaptic AT1 receptors in pithed rats

In the present study,we investigated the effects of angiotensin at 1-receptor blockers,kt3-671 and losartan,on the cardiac vagal neurotransmission in pithed rats. the bradycardia induced by vagal nerve stimulation (vns,at 5 hz) was potentiated significantly and dose-dependently by kt3-671 and also losartan. this enhancement effect of kt3-671 (10 mg/kg) was slightly potent than that of losartan (10 mg/kg). on the other hand,an angiotensin at2-receptor blocker,pd123319 (10 mg/kg),did not affect vns-induced bradycardia. kt3-671 and losartan did not affect the exogenous acetylcholine-evoked bradycardia. intravenous infusion of angii (100 ng/kg per min) attenuated the vns-induced bradycardia. this inhibitory effect of angii on bradycardia was restored by both kt3-671 and losartan. these results suggest that endogenous angii can have a tonic inhibitory effect on cardiac vagal transmission by stimulating the presynaptic at1 receptors not at 2 receptors. suppression of this mechanism by the at 1-receptor blockers causes the facilitation of acetylcholine release from vagal nerve endings. this acceleratory effect of at1-receptor blockers on cardiac vagal neurotransmission may contribute to the lack of reflex tachycardia following hypotension. © the japanese pharmacological society.