Inhibitory action of betaxolol, a beta 1-selective adrenoceptor antagonist, on voltage-dependent calcium channels in guinea-pig artery and vein.
1. The effects of betaxolol, (+/-)-1-[4-[2-(cyclopropylmethoxy) ethyl] phenoxy]-3-(isopropylamino)-2-propanol hydrochloride, a beta 1-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 2 mM Ca2+ 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 beta-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 beta-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 beta-adrenoceptor antagonist that has a direct inhibitory action on voltage-dependent Ca2+ channels in vascular smooth muscle cells.
Setoguchi
M
M
Second Department of Internal Medicine, Kyushu University, Faculty of Medicine, Fukuoka, Japan.
Ohya
Y
Y
Abe
I
I
Fujishima
M
M
D000818:Animals; D015784:Betaxolol / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008638:Mesenteric Arteries; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D011169:Portal Vein
D002121:Calcium Channel Blockers; D004110:Diltiazem; D009543:Nifedipine; D015784:Betaxolol