Angiotensin AT1–Receptor Blockers Enhance Cardiac Responses to Parasympathetic Nerve Stimulation via Presynaptic AT1 Receptors in Pithed Rats

Journal of Pharmacological Sciences

Akane Watanabe²  Masato Aoyama²  Takanori Arai¹  Fumiko Yamaki²  Yoshinobu Takata² 

[1] Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University, Japan;Department of Pharmacology, Ohu University School of Pharmaceutical Sciences, Japan

关键词: angiotensin AT1-receptor blocker;    angiotensin II;    vagal neurotransmission;    bradycardia;    rat heart;   

DOI  :  10.1254/jphs.12283FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(20)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.

【 授权许可】

Unknown