title: Angiotensin AT(1)-receptor blockers enhance cardiac responses to parasympathetic nerve stimulation via presynaptic AT(1) receptors in pithed rats.
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.
authors.affiliation: Department of Pharmacology, Ohu University School of Pharmaceutical Sciences, Japan. f-yamaki@pha.ohu-u.ac.jp
authors.forename: Fumiko
authors.initials: F
authors.lastname: Yamaki
authors.forename: Takanori
authors.initials: T
authors.lastname: Arai
authors.forename: Masato
authors.initials: M
authors.lastname: Aoyama
authors.forename: Akane
authors.initials: A
authors.lastname: Watanabe
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Takata
mesh_terms: D000109:Acetylcholine; D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001919:Bradycardia / Q000139:chemically induced / Q000503:physiopathology*; D004558:Electric Stimulation; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D007093:Imidazoles; C093160:KT3 671; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D017661:Receptors, Presynaptic; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D019808:Losartan; D000109:Acetylcholine