title: No-dependent vasodilation induced by nebivolol in coronary circulation is not mediated by beta-adrenoceptors or by 5 HT1A-receptors.
abstract: Nebivolol 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.
authors.affiliation: Department of Pharmacology, Jagiellonian University School of Medicine, ul. Grzegorzecka 16 31-531 Krakow, Poland. mfschlop@cyf-kr.edu.pl
authors.forename: S
authors.initials: S
authors.lastname: Chlopicki
authors.forename: V I
authors.initials: VI
authors.lastname: Kozlovski
authors.forename: R J
authors.initials: RJ
authors.lastname: Gryglewski
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D004983:Ethanolamines / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D000068577:Nebivolol; D009569:Nitric Oxide / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology; D013237:Stereoisomerism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D014665:Vasodilator Agents; D000068577:Nebivolol; D009569:Nitric Oxide