• S Chlopicki, V I Kozlovski, and R J Gryglewski.
• Department of Pharmacology, Jagiellonian University School of Medicine, ul. Grzegorzecka 16 31-531 Krakow, Poland. mfschlop@cyf-kr.edu.pl
• J. Physiol. Pharmacol. 2002 Dec 1; 53 (4 Pt 1): 615-24.

AbstractNebivolol is a unique beta1-adrenoceptor antagonist which possesses peripheral vasodilator properties dependent on endothelial NO. Nebivolol-induced release of NO was attributed to its L stereoisomer and to its ability to stimulate endothelial beta2, beta3 adrenoceptors or 5-HT1A receptors. Here, in the isolated guinea pig heart we analysed coronary vasodilator potency of L- and D-nebivolol and a possible role of beta2, beta3 adrenoceptors and 5-HT1A receptors in nebivolol-induced vasodilation. Surprisingly, we found that not only L-nebivolol (3-30 x 10(-6) M) but also D-nebivolol (3-30 x 10(-6) M) induced coronary vasodilation, and both responses were inhibited by L-NAME (10(-4) M). In contrast with the stereoisomers of nebivolol, atenolol at the equimolar concentrations did induce slight vasoconstriction. The nonselective beta1/beta2-adrenoceptor antagonist--nadolol (10(-5) M), the selective beta3-adrenoceptor antagonist--L 748337 (10(-6) M) and the 5 HT1A receptor antagonist--NAN 190 (5 x 10(-6) M), none of them inhibited coronary vasodilation induced by D- and L-nebivolol. In summary, in the isolated guinea pig heart both D- and L-nebivolol act as coronary vasodilators. Coronary vasodilation induced by stereoisomers of nebivolol is mediated by endothelium-derived NO and does not depend on beta2, beta3 adrenoceptors or 5 HT1A receptors.

33 keywords...

hide…