Pérez-Guerrero C, Suárez J, Herrera M D, Marhuenda E
Laboratorio de Farmacología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, España.
Pharmacol Res. 1997 Sep;36(3):237-42. doi: 10.1006/phrs.1997.0221.
The vasodilating effects of tetrazepam (1,4-benzodiazepine derivative) were studied and compared with those of the K-channel activator, cromakalim and the Ca-channel blocker, diltiazem, in rat aorta smooth muscle and on the spontaneous contractile activity of the rat portal vein. In the aorta, tetrazepam (3 x 10(-7)-10(-4) M) and diltiazem (10(-8)-3 x 10(-6) M) concentration-dependently relaxed aortic rings contracted by 30 mM as well as 80 m KCl. Although cromakalim (10(-8)-3 x 10(-6) M) concentration-dependently relaxed aortic rings contracted by 30 mM KCl, it did not relax those contrated by 80 mm KCl. In the presence of the ATP-sensitive K-channel blocker, glibenclamide (10(-6) and 3 x 10(-6) M), 30 mM KCl concentration-response curves for the relaxant effect of tetrazepam and diltiazem were unaffected but cromakalim caused a progressive shift of these curves upwards. In the portal vein, tetrazepam inhibited spontaneous contractions, decreased amplitude and increased frequency. Similar behaviour was shown with diltiazem (10(-8)-10(-5) M) and in both cases, pre-treatment with glibenclamide (10(-6) M) was ineffective. Although cromakalim (10(-5)-10(-6) M) decreased both amplitude and frequency, this effect was blocked by glibenclamide. These results indicate that the vasodilator action of tetrazepam is not mediated to the opening of ATP-sensitive K-channels, unlike cromakalim. This may be mediated, like those of diltiazem, by the blockade of calcium movements across the cell membrane.
研究了四氮唑安定（一种1,4 - 苯二氮䓬衍生物）的血管舒张作用，并将其与钾通道激活剂克罗卡林和钙通道阻滞剂地尔硫䓬在大鼠主动脉平滑肌以及大鼠门静脉自发收缩活动方面的作用进行了比较。在主动脉中，四氮唑安定（3×10⁻⁷ - 10⁻⁴ M）和地尔硫䓬（10⁻⁸ - 3×10⁻⁶ M）能浓度依赖性地舒张由30 mM以及80 mM KCl引起收缩的主动脉环。虽然克罗卡林（10⁻⁸ - 3×10⁻⁶ M）能浓度依赖性地舒张由30 mM KCl引起收缩的主动脉环，但对由80 mM KCl引起收缩的主动脉环却无舒张作用。在存在ATP敏感性钾通道阻滞剂格列本脲（10⁻⁶和3×10⁻⁶ M）的情况下，四氮唑安定和地尔硫䓬对30 mM KCl的舒张作用的浓度 - 反应曲线未受影响，但克罗卡林使这些曲线逐渐上移。在门静脉中，四氮唑安定抑制自发收缩，降低幅度并增加频率。地尔硫䓬（10⁻⁸ - 10⁻⁵ M）也表现出类似行为，且在两种情况下，用格列本脲（10⁻⁶ M）预处理均无效。虽然克罗卡林（10⁻⁵ - 10⁻⁶ M）降低了幅度和频率，但这种作用被格列本脲阻断。这些结果表明，与克罗卡林不同，四氮唑安定的血管舒张作用不是通过ATP敏感性钾通道的开放介导的。这可能像地尔硫䓬一样，是通过阻断钙跨细胞膜的移动介导的。
