Angiotensin AT(1)-Receptor Blockers Enhance Cardiac Responses to Parasympathetic Nerve Stimulation via Presynaptic AT(1) Receptors in Pithed Rats

作者：Yamaki Fumiko^*; Arai Takanori; Aoyama Masato; Watanabe Akane; Takata Yoshinobu

来源：Journal of Pharmacological Sciences, 2013, 122(1): 28-33.

DOI：10.1254/jphs.12283FP

• angiotensin AT(1)-receptor blocker
• angiotensin II
• vagal neurotransmission
• bradycardia
• rat heart

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 AT(2)-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 AT(1) 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 AT(1)-receptor blockers on cardiac vagal neurotransmission may contribute to the lack of reflex tachycardia following hypotension.

• 出版日期2013-5