ABSTRACT
In the present study, we investigated the effects of angiotensin AT1-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 AT2 receptors. Suppression of this mechanism by the AT1-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.
Subject(s)
Angiotensin II Type 1 Receptor Blockers/pharmacology , Bradycardia/physiopathology , Receptor, Angiotensin, Type 1/physiology , Receptors, Presynaptic/physiology , Vagus Nerve/drug effects , Acetylcholine , Angiotensin II/pharmacology , Angiotensin II Type 2 Receptor Blockers/pharmacology , Animals , Bradycardia/chemically induced , Electric Stimulation , Imidazoles/pharmacology , Losartan/pharmacology , Male , Pyridines/pharmacology , Rats , Rats, Wistar , Tetrazoles/pharmacology , Vagus Nerve/physiologyABSTRACT
The effect of captopril on neurally evoked bradycardia and tachycardia was investigated in pithed rats. Captopril enhanced the vagal nerve stimulation-evoked bradycardia. Angiotensin I reduced the vagal bradycardia, which was reversed by subsequent administration of captopril. Bradykinin did not affect the neurally evoked bradycardia. Captopril and angiotensin I affected neither the exogenous acetylcholine-evoked bradycardia nor the sympathetic nerve stimulation-evoked tachycardia. These results suggest that the interruption of angiotensin II formation by captopril causes less presynaptic inhibition of acetylcholine release via angiotensin II receptors without affecting cardiac sympathetic neurotransmission.