Author + information
- Atsuo Nomura,
- Satoshi Nishioka,
- Waka Uehashi,
- Ryuji Kato,
- Yoshikatsu Okada,
- Nobukazu Ishizaka,
- Yasuo Matsumura and
- Tetsuya Hayashi
We have reported that intermittent hypoxic stress, which is relevant to sleep apnea syndrome (SAS), increases oxidative stress and induces left ventricular (LV) remodeling. Celiprolol, a ß1-selective adrenoreceptor blocker, has been known to possess not only anti-hypertensive but also anti-oxidative effects by releasing nitric oxide. The aim of this study was to examine the hypothesis that celiprolol might attenuate the ventricular remodeling induced by intermittent hypoxia in mice.
Male C57BL/6J mice at 8 weeks of age were exposed to intermittent hypoxia (30 seconds exposure to 5% oxygen, followed by 30 seconds exposure to 21% oxygen) for 8 hours/day during the daytime, or maintained under normoxic conditions. Animals were treated with celiprolol (100 mg/kg/day), atenolol (50 mg/kg/day), or vehicle for 10 days.
Hypoxic stress caused fluctuation of blood pressure, and increased biventricular cardiomyocyte diameter and perivascular fibrosis, associated with increased 4-hydroxy-2-nonenal protein, superoxide production, and tumor necrosis factor-α and brain natriuretic peptide mRNA in the LV myocardium. Celiprolol as well as atenolol significantly suppressed the blood pressure fluctuation. Furthermore, celiprolol, but not atenolol, enhanced eNOS expression, reduced oxidative stress and superoxide production, consequently attenuating the hypoxia-induced LV remodeling in mice.
This study suggests that aggressive treatment with celiprolol might efficacious to prevent cardiovascular events in borderline hypertensive patients associated with SAS.
Poster Sessions, Expo North
Saturday, March 09, 2013, 3:45 p.m.-4:30 p.m.
Session Title: Novel Therapeutic Targets in Hearts Failure
Abstract Category: 16. Heart Failure: Basic
Presentation Number: 1176-297
- 2013 American College of Cardiology Foundation