Bessho H, Suzuki J, Tobe A
Pharmaceuticals Laboratory, Mitsubishi Kasei Corporation, Yokohama, Japan.
Jpn J Pharmacol. 1991 Mar;55(3):351-8. doi: 10.1254/jjp.55.351.
The effects of betaxolol on isolated rat arteries and the modes of action were investigated. Betaxolol (10(-5)-10(-3) M) relaxed the 80 mM K(+)-induced contraction of aortic strips concentration-dependently. The 50% inhibitory concentration of betaxolol in the K(+)-induced contraction was 3 times higher than that of papaverine and about 3 times lower than that of bunitrolol. The relaxations by betaxolol were also demonstrated in renal, mesenteric and femoral arteries. Betaxolol (3 x 10(-6) M-10(-4) M) produced rightward parallel shifts of the concentration-response curves for Ca2+ in the K(+)-depolarized aortic strips. On the other hand, betaxolol produced downward shifts as well as rightward shifts of the concentration-response curves for norepinephrine, 5-HT and angiotensin II. In K(+)-depolarized aortic strips, the cytosolic Ca2+ concentration measured with a fluorescent indicator, fura-2, was decreased by betaxolol (10(-4) M) almost concomitantly with the loss of tention. An elevation of external Ca2+ from 2.5 mM to 10 mM restored both the cytosolic Ca2+ concentration and tention. The relaxations of arteries induced by betaxolol were not influenced by glybenclamide, methylene blue, indomethacin or removal of the endothelium. These results suggest that betaxolol possesses a direct vasodilating action, and the action may be due to the inhibition of Ca2+ influx across the cell membrane.
研究了倍他洛尔对离体大鼠动脉的作用及其作用方式。倍他洛尔（10(-5)-10(-3)M）浓度依赖性地松弛80mM K(+)诱导的主动脉条收缩。倍他洛尔在K(+)诱导收缩中的50%抑制浓度比罂粟碱高3倍，比布尼洛尔低约3倍。倍他洛尔对肾动脉、肠系膜动脉和股动脉也有舒张作用。倍他洛尔（3×10(-6)M-10(-4)M）使K(+)去极化主动脉条中Ca2+浓度-反应曲线向右平行移动。另一方面，倍他洛尔使去甲肾上腺素、5-羟色胺和血管紧张素II的浓度-反应曲线向下和向右移动。在K(+)去极化主动脉条中，用荧光指示剂fura-2测定的胞质Ca2+浓度几乎与张力丧失同时被倍他洛尔（10(-4)M）降低。细胞外Ca2+从2.5mM升高到10mM可恢复胞质Ca2+浓度和张力。倍他洛尔诱导的动脉舒张不受格列本脲、亚甲蓝、吲哚美辛或去除内皮的影响。这些结果表明，倍他洛尔具有直接的血管舒张作用，且该作用可能是由于抑制了Ca2+跨细胞膜内流。
