Carvedilol exerts vasodilating action in canine coronary arteries likely by inhibiting calcium influx through potential-operated calcium channels, though at concentrations higher than needed for beta-blockade.
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 et al. (1989) studied this question.