Release of endothelial nitric oxide in coronary arteries by celiprolol, a beta(1)-adrenoceptor antagonist: possible clinical relevance

Mechanisms underlying celiprolol-induced vasodilatation were analyzed in is olated porcine coronary arteries. Celiprolol induced dose-related relaxatio n of the artery rings with endothelium, an effect which was suppressed by N G-nitro-L-arginine methylester (L-NAME), nitric oxide (NO) scavenger, guany late cyclase inhibitor, endothelium denudation, and removal of Ca2+. L-NAME contracted, and superoxide dismutase relaxed, the arteries only when the e ndothelium was preserved. Neither superoxide dismutase nor P-adrenoceptor a ntagonists changed celiprolol-induced relaxations. Celiprolol increased the cyclic GMP content in the tissue. The release of NO from endothelium, esti mated by the extracellular production of cyclic GMP in arteries incubated i n medium containing guanylate cyclase and GTP, was augmented by celiprolol, and L-NAME abolished this action of celiprolol. It is concluded that celip rolol elicits relaxation by acting on sites other than P-adrenoceptors in t he endothelium and by releasing NO, which activates soluble guanylate cycla se in smooth muscle and produces cyclic GMP. Scavenging of superoxide anion s from the endothelium does not seem to account for the induced relaxation. (C) 2001 Elsevier Science B.V. All rights reserved.