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Inhibitory action of betaxolol, a β‐selective adrenoceptor antagonist, on voltage‐dependent calcium channels in guinea‐pig artery and vein
Author(s) -
Setoguchi Motoko,
Ohya Yusuke,
Abe Isao,
Fujishima Masatoshi
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb16339.x
Subject(s) - betaxolol , nifedipine , inhibitory postsynaptic potential , diltiazem , vascular smooth muscle , antagonist , calcium channel , pharmacology , chemistry , superior mesenteric artery , patch clamp , prazosin , endocrinology , electrophysiology , medicine , calcium , receptor , smooth muscle , timolol , surgery , intraocular pressure
1 The effects of betaxolol, (±)‐l‐[4‐[2‐(cyclopropylmethoxy) ethyl] phenoxy]‐3‐(isopropylamino)‐2‐propanol hydrochloride, a β 1 ‐selective adrenoceptor antagonist, on voltage‐dependent Ca 2+ 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. Ca 2+ channel currents were recorded with bath solutions contained 10 mM Ba 2+ for arterial cells and 2mMCa 2+ for venous cells. 2 Betaxolol inhibited Ca 2+ 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 Ca 2+ channel currents in portal vein cells. Propranolol did not inhibit the currents. Thus the inhibitory action of betaxolol on Ca 2+ channel currents was independent of the β‐adrenoceptor. 3 The inhibitory action of betaxolol on Ca 2+ 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 Ca 2+ 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 Ca 2+ channels in vascular smooth muscle cells.