Weir S W, Weston A H
Br J Pharmacol. 1986 May;88(1):121-8. doi: 10.1111/j.1476-5381.1986.tb09478.x.
The effects of the antihypertensive agent BRL 34915 on a variety of responses of the aorta and portal vein of the rat have been compared with those of nicorandil. On portal vein, BRL 34915 (0.01-50 X 10(-6) M) and nicorandil (0.1-500 X 10(-6) M) abolished spontaneous mechanical activity and reduced mechanical responses to noradrenaline (0.1-100 X 10(-6) M) and K+ (5-20 X 10(-3) M) but had little inhibitory effect on responses to K+ (40-80 X 10(-3) M). The onset of the reduced responses to noradrenaline was delayed by both agents. On portal vein, BRL 34915 (0.1-50 X 10(-6) M) and nicorandil (0.5-500 X 10(-6) M) abolished spontaneous electrical and mechanical activity, hyperpolarized the smooth muscle cells to a value close to their calculated potassium equilibrium potential and increased the 86Rb efflux rate coefficient. On aorta, BRL 34915 (0.2-0.8 X 10(-6) M) and nicorandil (8-32 X 10(-6) M) reduced mechanical responses to noradrenaline (0.001-1 X 10(-6) M) and K+ (5-20 X 10(-3) M) but had little inhibitory effect on responses to K+ (40-80 X 10(-3) M). On aorta, BRL 34915 (0.2-0.8 X 10(-6) M) increased the 86Rb efflux rate coefficient whereas nicorandil (8-32 X 10(-6) M) was without effect. It is concluded that the inhibitory actions of BRL 34915 on both aorta and portal vein result from the opening of membrane potassium channels. The resulting membrane shunt inhibits the effects of excitatory agents. The inhibitory effects of nicorandil result from a combination of the opening of potassium channels together with an additional, undefined action.
已将抗高血压药物BRL 34915对大鼠主动脉和门静脉各种反应的作用与尼可地尔的作用进行了比较。在门静脉上，BRL 34915（0.01 - 50×10⁻⁶ M）和尼可地尔（0.1 - 500×10⁻⁶ M）可消除自发性机械活动，并降低对去甲肾上腺素（0.1 - 100×10⁻⁶ M）和K⁺（5 - 20×10⁻³ M）的机械反应，但对K⁺（40 - 80×10⁻³ M）的反应几乎没有抑制作用。两种药物都延迟了对去甲肾上腺素反应降低的起效时间。在门静脉上，BRL 34915（0.1 - 50×10⁻⁶ M）和尼可地尔（0.5 - 500×10⁻⁶ M）可消除自发性电活动和机械活动，使平滑肌细胞超极化至接近其计算出的钾平衡电位的值，并增加⁸⁶Rb外流速率系数。在主动脉上，BRL 34915（0.2 - 0.8×10⁻⁶ M）和尼可地尔（8 - 32×10⁻⁶ M）可降低对去甲肾上腺素（0.001 - 1×10⁻⁶ M）和K⁺（5 - 20×10⁻³ M）的机械反应，但对K⁺（40 - 80×10⁻³ M）的反应几乎没有抑制作用。在主动脉上，BRL 34915（0.2 - 0.8×10⁻⁶ M）增加了⁸⁶Rb外流速率系数，而尼可地尔（8 - 32×10⁻⁶ M）则无此作用。得出结论，BRL 34915对主动脉和门静脉的抑制作用是由膜钾通道开放引起的。由此产生的膜分流抑制了兴奋性药物的作用。尼可地尔的抑制作用是由钾通道开放与另一种未明确的作用共同导致的。
