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.
摘要
使用膜片钳技术的全细胞变体，研究了β1选择性肾上腺素能受体拮抗剂盐酸倍他洛尔（±）-1-[4-[2-（环丙基甲氧基）乙基]苯氧基]-3-（异丙氨基）-2-丙醇对豚鼠肠系膜动脉和门静脉单个平滑肌细胞中电压依赖性Ca2+通道的影响。动脉细胞的浴液含10 mM Ba2+，静脉细胞的浴液含2 mM Ca2+，记录Ca2+通道电流。2. 倍他洛尔在肠系膜动脉细胞和门静脉细胞中均剂量依赖性地抑制Ca2+通道电流。两种异构体，（+）-倍他洛尔和（-）-倍他洛尔（相对β拮抗效能分别为0.1和1），对门静脉细胞中Ca2+通道电流的抑制效力相似。普萘洛尔不抑制电流。因此，倍他洛尔对Ca2+通道电流的抑制作用与β肾上腺素能受体无关。3. 在肠系膜动脉细胞中，比较了倍他洛尔对Ca2+通道电流的抑制作用与地尔硫卓和硝苯地平的抑制作用。所有药物的电流抑制均取决于刺激频率（使用依赖性阻滞）。所有药物还加速了电流衰减，并使电压依赖性失活曲线向负方向移动。4. 总之，倍他洛尔抑制血管平滑肌细胞中的Ca2+通道电流。其抑制作用方式与地尔硫卓和硝苯地平相似。我们的结果表明，倍他洛尔是一种独特的β肾上腺素能受体拮抗剂，对血管平滑肌细胞中的电压依赖性Ca2+通道具有直接抑制作用。
