Vascular Effects of Carvedilol, a New β-Adrenoceptor Antagonist with Vasodilating Properties, in Isolated Canine Coronary Artery

Summary: The pharmacologic properties of carvedilol, a β-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 ≥3 × 10−6M, carvedilol significantly inhibited the contractile response to high [K+]o. Compared with the inhibitory effect on the KCI-induced contraction, the drug was less effective in suppressing the contraction induced by prostaglandin F2α (PGF2α). In addition, carvedilol (10−7 to 3 × 10−5M) 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 PGF2α 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 β-adrenoceptor antagonism in canine coronary artery.