Vasodilator effects of nebivolol in a rat model of hypertension and a rabbit model of congestive heart failure.
Both hypertension and congestive heart failure are characterized by a reduced vasodilatory capacity. In both conditions, the impairment of endothelial function is mainly the result of a reduced nitric oxide availability. The highly beta1-selective third-generation adrenoceptor blocker nebivolol displays additional endothelium-dependent vasodilating actions in humans as well as in animal models. In this study, we investigated whether these vasodilating properties of nebivolol are preserved in conditions with endothelial dysfunction. The vasodilatory effects of nebivolol were compared with those of the muscarinic agonist methacholine in isolated aortic rings obtained from spontaneous hypertensive rats and rabbits with experimental heart failure. The methacholine-induced responses were attenuated in aortic rings from both spontaneous hypertensive rats and congestive heart failture rabbits (42+/-6% and 25+/-3% vs. 89+/-3% and 54+/-7% for controls, respectively; P<0.05, n=6-13), indicating an endothelial dysfunction in these preparations. In contrast, nebivolol-induced vasorelaxation remained unaffected in both preparations when compared to control preparations (40+/-12% and 43+/-6% vs. 52+/-8% and 50+/-13% for controls, respectively; P>0.05, n=6-13). These results implicate that the favorable hemodynamic profile of nebivolol may be preserved in patients with hypertension or congestive heart failure despite an impaired endothelial function.
Department of Pharmacology and Pharmacotherapy, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Annemieke A
AA
de Groot
Marie-Jeanne
MJ
Mathy
Pieter A
PA
van Zwieten
Stephan L M
SL
Peters
D000818:Animals; D001013:Aorta, Thoracic; D001578:Benzopyrans / Q000494:pharmacology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D004983:Ethanolamines / Q000494:pharmacology*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D000068577:Nebivolol; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D004983:Ethanolamines; D018721:Muscarinic Agonists; D014665:Vasodilator Agents; D000068577:Nebivolol; D016210:Methacholine Chloride