title: Celiprolol reduces oxidative stress and attenuates left ventricular remodeling induced by hypoxic stress in mice.
abstract: We have previously reported that intermittent hypoxic stress, which is relevant to sleep apnea syndrome (SAS), increases oxidative stress and induces left ventricular (LV) remodeling. Celiprolol, a β1-selective adrenoreceptor blocker, is known to have not only an antihypertensive effect but also an antioxidant effect through releasing nitric oxide. The aim of this study was to examine the hypothesis that celiprolol might ameliorate the LV remodeling induced by intermittent hypoxia through its antioxidant effect. Male C57BL/6J mice (8 weeks old) were exposed to intermittent hypoxia (30 s of 5% oxygen followed by 30 s of 21% oxygen) for 8 h day(-1) during the daytime for 10 consecutive days or were maintained under normoxic conditions. Animals were treated with either celiprolol (100 mg kg(-1) day(-1) by gavage) or vehicle. Hypoxic stress caused fluctuations in blood pressure (BP), an increase in the mean cardiomyocyte diameter, perivascular fibrosis and a decrease in endothelial nitric oxide synthase (eNOS) expression. These changes were associated with increased levels of 4-hydroxy-2-nonenal protein, superoxide, tumor necrosis factor-α mRNA and brain natriuretic peptide mRNA in the LV myocardium. Celiprolol significantly suppressed BP fluctuation, restored eNOS expression and reduced oxidative stress and superoxide production, thus ameliorating hypoxia-induced LV remodeling in mice. These findings suggest that treatment with celiprolol might prevent cardiovascular events in borderline hypertensive patients with SAS.
authors.affiliation: Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishioka
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Atsuo
authors.initials: A
authors.lastname: Nomura
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kato
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Miyamura
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Okada
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Ishizaka
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hayashi
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D017272:Celiprolol / Q000494:pharmacology* / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D013481:Superoxides; D017272:Celiprolol