Kashiwabara T, Nakajima S, Izawa T, Fukushima H, Nishikori K
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
Eur J Pharmacol. 1991 Apr 10;196(1):1-7. doi: 10.1016/0014-2999(91)90401-b.
The characteristics of KRN2391, a novel vasodilator, were studied in rat isolated aorta. The effects of KRN2391, cromakalim, pinacidil and nifedipine on the contractions induced by 20, 40 and 80 mM K+ and by 10(-7) M norepinephrine (NE) were measured first. KRN2391, cromakalim and pinacidil selectively inhibited the contractions induced by 20 mM K+ and NE rather than those induced by high concentrations of K+. Nifedipine could not completely inhibit the NE-induced contractions. The vasorelaxant effect of KRN2391 was inhibited by K+ channel blockers and guanylate cyclase inhibitors. KRN2391, cromakalim and pinacidil increased the 86Rb efflux rate coefficient. Thus, KRN2391 exhibits a vasodilator profile similar to that of the K+ channel openers and induces an increase in 86Rb efflux. It is suggested that opening of the membrane K+ channels may be partly involved in the vasorelaxant mechanism of KRN2391.
在大鼠离体主动脉中研究了新型血管扩张剂KRN2391的特性。首先测定了KRN2391、克罗卡林、匹那地尔和硝苯地平对20、40和80 mM钾离子（K+）以及10^(-7) M去甲肾上腺素（NE）诱导的收缩的影响。KRN2391、克罗卡林和匹那地尔选择性抑制20 mM K+和NE诱导的收缩，而非高浓度K+诱导的收缩。硝苯地平不能完全抑制NE诱导的收缩。KRN2391的血管舒张作用被钾通道阻滞剂和鸟苷酸环化酶抑制剂抑制。KRN2391、克罗卡林和匹那地尔增加了86Rb外流速率系数。因此，KRN2391表现出与钾通道开放剂相似的血管扩张特性，并诱导86Rb外流增加。提示膜钾通道开放可能部分参与了KRN2391的血管舒张机制。
