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Inhibitory action of betaxolol, a β‐selective adrenoceptor antagonist, on voltage‐dependent calcium channels in guinea‐pig artery and vein

1 The effects of betaxolol, (±)‐l‐[4‐[2‐(cyclopropylmethoxy) ethyl] phenoxy]‐3‐(isopropylamino)‐2‐propanol hydrochloride, a β1‐selective adrenoceptor antagonist, on voltage‐dependent Ca2+ channels were investigated in single smooth muscle cells from guinea‐pig mesenteric artery and portal vein using a whole‐cell variant of the patch‐clamp technique. Ca2+ channel currents were recorded with bath solutions contained 10 mM Ba2+ for arterial cells and 2mMCa2+ for venous cells. 2 Betaxolol inhibited Ca2+ channel currents dose‐dependently in both mesenteric artery cells and portal vein cells. The two isomers, (+)‐betaxolol and (−)−betaxolol (relative β‐antagonistic efficacies of 0.1 and 1, respectively), had similar potencies for inhibiting Ca2+ channel currents in portal vein cells. Propranolol did not inhibit the currents. Thus the inhibitory action of betaxolol on Ca2+ channel currents was independent of the β‐adrenoceptor. 3 The inhibitory action of betaxolol on Ca2+ channel currents was compared with that of diltiazem and of nifedipine in mesenteric artery cells. The current inhibition depended on the stimulation frequency with all drugs (use‐dependent block). All drugs also accelerated the current decay and shifted the voltage‐dependent inactivation curve in a negative direction. 4 In conclusion, betaxolol inhibited Ca2+ channel currents in vascular smooth muscle cells. The mode of inhibitory action was similar to that of diltiazem and nifedipine. Our results suggest that betaxolol is a unique β‐adrenoceptor antagonist that has a direct inhibitory action on voltage‐dependent Ca2+ channels in vascular smooth muscle cells.