Vascular effects of carvedilol, a new beta-adrenoceptor antagonist with vasodilating properties, in isolated canine coronary artery.
The pharmacologic properties of carvedilol, a beta-adrenoceptor antagonist with vasodilating activity, were investigated in isolated canine coronary artery ring preparations. Carvedilol competitively antagonized the relaxations caused by isoproterenol in 40 mM K+-depolarized preparations and its pA, value was 9.70 +/- 0.08. At concentrations greater than or equal to 3 x 10(-6) M, carvedilol significantly inhibited the contractile response to high [K+]o. Compared with the inhibitory effect on the KCl-induced contraction, the drug was less effective in suppressing the contraction induced by prostaglandin F2 alpha (PGF2 alpha). In addition, carvedilol (10(-7) to 3 x 10(-5) M) suppressed the contraction produced by Bay K 8644, a Ca2+ channel agonist. The concentration-response curve for Bay K 8644 was shifted downward by carvedilol in a concentration-dependent manner. The drug also produced a concentration-dependent inhibitory effect on the 4-aminopyridine-induced rhythmic contractions in a similar fashion to the Ca2+ channel antagonists. Carvedilol was ineffective in suppressing the contractions induced by PGF2 alpha in Ca2+-free solution and by A-23187. The results suggest that carvedilol exerts a vasodilating action possibly by inhibiting Ca2+ influx through potential-operated Ca2+ channels, although the concentrations required for producing the vasodilation are much higher than that for the beta-adrenoceptor antagonism in canine coronary artery.
Hattori
Y
Y
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Nakaya
H
H
Endou
M
M
Nakao
Y
Y
Kanno
M
M
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D015220:Calcium Channels; D002227:Carbazoles; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol