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Celiprolol stimulates endothelial nitric oxide synthase expression and improves myocardial remodeling in

N Kobayashi1, Y Mori, S Nakano

  • 1Department of Hypertension and Cardiorenal Medicine, Institute for Medical Science, Dokkyo University School of Medicine, Mibu, Tochigi, Japan. a-fukuda@dokkyomed.ac.jp

Journal of Hypertension
|May 2, 2001
PubMed

Insights

Celiprolol treatment increased nitric oxide synthase expression in the hearts of hypertensive rats. This improved cardiac remodeling, suggesting a potential therapeutic benefit for hypertension.

Area of Science:

  • Cardiovascular Physiology
  • Pharmacology
  • Molecular Biology

Background:

  • Endothelium-dependent vasodilation is often impaired in hypertension, potentially due to reduced nitric oxide (NO).
  • The effect of beta-adrenoceptor antagonists on endothelial NO synthase (eNOS) expression in the heart is not well understood.
  • Investigating celiprolol's impact on eNOS and cardiac remodeling in hypertension is crucial.

Purpose of the Study:

  • To investigate the long-term effects of celiprolol on eNOS expression in the left ventricle of DOCA-salt hypertensive rats.
  • To evaluate the relationship between celiprolol-induced changes in eNOS and myocardial remodeling.
  • To determine if celiprolol, at a subdepressor dose, can ameliorate cardiac structural changes in hypertension.

Main Methods:

  • DOCA-salt hypertension was induced in rats via DOCA injections and saline consumption post-nephrectomy.
  • Rats received either celiprolol (10 mg/kg/day) or vehicle for 5 weeks.
  • Sham-operated rats served as controls; measurements included eNOS mRNA, protein, NOS activity, and cardiac remodeling markers.

Main Results:

  • Hypertensive rats treated with celiprolol showed significantly increased left ventricular eNOS mRNA, protein levels, and NOS activity compared to vehicle-treated rats.
  • Celiprolol treatment significantly improved cardiac remodeling, including reduced wall-to-lumen ratio, perivascular fibrosis, myocardial fibrosis, and type I collagen mRNA.
  • Blood pressure levels were similar between celiprolol and vehicle groups, indicating effects beyond simple blood pressure reduction.

Conclusions:

  • Subdepressor doses of celiprolol significantly ameliorated myocardial remodeling in DOCA-salt hypertensive rats.
  • The beneficial effects of celiprolol on cardiac remodeling may be attributed to increased eNOS expression in the left ventricle.
  • Celiprolol demonstrates potential as a therapeutic agent for managing hypertensive cardiac complications through mechanisms involving NO pathways.
Abstract

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