Endothelial beta3-adrenoreceptors mediate nitric oxide-dependent vasorelaxation of coronary microvessels in response to the third-generation beta-blocker nebivolol

The therapeutic effects of nonspecific beta-blockers are limited by vasoconstriction, thus justifying the interest in molecules with ancillary vasodilating properties. Nebivolol is a selective beta1-adrenoreceptor antagonist that releases nitric oxide (NO) through incompletely characterized mechanis...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 2005-08, Vol.112 (8), p.1198-1205
Main Authors: Dessy, Chantal, Saliez, Julie, Ghisdal, Philippe, Daneau, Géraldine, Lobysheva, Irina I, Frérart, Françoise, Belge, Catharina, Jnaoui, Karima, Noirhomme, Philippe, Feron, Olivier, Balligand, Jean-Luc
Format: Article
Language:English
Subjects:
Adrenergic beta-Antagonists - pharmacology
Animals
Benzopyrans - pharmacology
Calcium - metabolism
Coronary Circulation - drug effects
Coronary Circulation - physiology
Endothelium, Vascular - metabolism
Ethanolamines - pharmacology
Humans
Male
Mice
Microcirculation - drug effects
Microcirculation - physiology
Nebivolol
Nitrates - metabolism
Nitric Oxide - metabolism
Nitric Oxide Synthase Type III - metabolism
Nitrites - metabolism
Phosphorylation
Rats
Rats, Wistar
Receptors, Adrenergic, beta-3 - metabolism
Vasodilation - drug effects
Vasodilation - physiology
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Summary:The therapeutic effects of nonspecific beta-blockers are limited by vasoconstriction, thus justifying the interest in molecules with ancillary vasodilating properties. Nebivolol is a selective beta1-adrenoreceptor antagonist that releases nitric oxide (NO) through incompletely characterized mechanisms. We identified endothelial beta3-adrenoreceptors in human coronary microarteries that mediate endothelium- and NO-dependent relaxation and hypothesized that nebivolol activates these beta3-adrenoreceptors. Nebivolol dose-dependently relaxed rodent coronary resistance microarteries studied by videomicroscopy (10 micromol/L, -86+/-6% of prostaglandin F2alpha contraction); this was sensitive to NO synthase (NOS) inhibition, unaffected by the beta(1-2)-blocker nadolol, and prevented by the beta(1-2-3)-blocker bupranolol (P
ISSN:1524-4539