title: A protective role of Nox1/NADPH oxidase in a mouse model with hypoxia-induced bradycardia.
abstract: Although it has been reported that endotoxin-induced expression of Nox1 in the heart contributes to apoptosis in cardiomyocytes, functional role of Nox1 at the physiological expression level has not been elucidated. The aim of this study was to clarify the role of Nox1 under a hypoxic condition using wild-type (WT, Nox1(+/Y)) and Nox1-deficient (Nox1(-/Y)) mice. ECG recordings from anesthetized mice revealed that Nox1(-/Y) mice were more sensitive to hypoxia, resulting in bradycardia, compared to WT mice. Atrial and ventricular electrocardiograms recorded from Langendorff-perfused hearts revealed that hypoxic perfusion more rapidly decreased heart rate in Nox1(-/Y) hearts compared with WT hearts. Sinus node recovery times measured under a hypoxic condition were prolonged more markedly in the Nox1(-/Y) hearts. Sinoatrial node dysfunction of Nox1(-/Y) hearts during hypoxia was ameriolated by the pre-treatment with the Ca(2+) channel blocker nifedipine or the K(+) channel opener pinacidil. Spontaneous action potentials were recorded from enzymatically-isolated sinoatrial node (SAN) cells under a hypoxic condition. There was no significant difference in the elapsed times from the commencement of hypoxia to asystole between WT and Nox1(-/Y) SAN cells. These findings suggest that Nox1 may have a protective effect against hypoxia-induced SAN dysfunction.
authors.affiliation: Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba, Japan; Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Akiteru
authors.initials: A
authors.lastname: Kojima
authors.affiliation: Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nishida
authors.affiliation: Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Reien
authors.affiliation: Department of Pharmacology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Iwata
authors.affiliation: Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shirayama
authors.affiliation: Department of Pharmacology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Yabe-Nishimura
authors.affiliation: Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba, Japan. Electronic address: nakaya@faculty.chiba-u.jp.
authors.forename: Haruaki
authors.initials: H
authors.lastname: Nakaya
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001919:Bradycardia / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004562:Electrocardiography; D006339:Heart Rate; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology; D066298:In Vitro Techniques; D049990:Membrane Transport Modulators / Q000494:pharmacology / Q000627:therapeutic use; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009247:NADH, NADPH Oxidoreductases / Q000502:physiology*; D000074624:NADPH Oxidase 1; D009543:Nifedipine / Q000494:pharmacology / Q000627:therapeutic use; D020110:Pinacidil / Q000494:pharmacology / Q000627:therapeutic use; D012848:Sinoatrial Block / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D012849:Sinoatrial Node / Q000166:cytology / Q000503:physiopathology
chemical_list: D002121:Calcium Channel Blockers; D049990:Membrane Transport Modulators; D020110:Pinacidil; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; C000614711:NOX1 protein, mouse; D009543:Nifedipine
keywords: Hypoxia; NADPH oxidase; Sinoatrial node