Nebivolol induces endothelium-dependent relaxations of canine coronary arteries.
Nebivolol is a new beta 1-antagonist that acutely reduces arterial blood pressure without depressing cardiac function. The present study was designed to determine the effect of nebivolol on coronary arteries. Rings of canine left anterior descending coronary (LAD) artery with or without endothelium were suspended in organ chambers and the isometric tension was recorded. In some experiments, the transmembrane potential of the smooth muscle cells was recorded by electrophysiological methods. During contractions to prostaglandin F2 alpha, nebivolol induced concentration-dependent relaxations of the coronary arteries. The enantiomer, l-nebivolol, also induced comparable relaxations; however, d-nebivolol induced smaller relaxations. The relaxations induced by nebivolol and its enantiomer were significantly larger in tissues with than in those without endothelium. The differences between tissues with and without endothelium were abolished by nitro-L-arginine (3 x 10(-5) M) or methylene blue (10(-5) M). The nebivolol-induced relaxations were not affected by indomethacin (10(-5) M), phentolamine (5 x 10(-6) M), propranolol (5 x 10(-6) M), or methysergide (3 x 10(-6) M). Nebivolol at a subthreshold concentration for inducing relaxation (3 x 10(-7) M) did not significantly affect endothelium-dependent relaxations to acetylcholine but potentiated ADP-induced endothelium-dependent relaxations. The potentiation is stereoselective for l-nebivolol. Nebivolol induced a small hyperpolarization of the coronary smooth muscle with endothelium (1 mV).(ABSTRACT TRUNCATED AT 250 WORDS)
Gao
Y S
YS
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, Texas 77030.
Nagao
T
T
Bond
R A
RA
Janssens
W J
WJ
Vanhoutte
P M
PM
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D000068577:Nebivolol
D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D015237:Dinoprost