KRN2391、尼可地尔和克罗卡林在犬肾动脉中的作用机制差异。

Dissimilarity in the mechanisms of action of KRN2391, nicorandil and cromakalim in canine renal artery.

作者信息

Kasai H, Fukata Y, Harada K, Fukushima H, Ogawa N

机构信息

Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd., Gunma, Japan.

出版信息

J Pharm Pharmacol. 1993 Mar;45(3):222-4. doi: 10.1111/j.2042-7158.1993.tb05538.x.

DOI:10.1111/j.2042-7158.1993.tb05538.x

PMID:8097782

Abstract

In the present study, we examined the mode of action of KRN2391 (N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide monomethanesulphonate) in isolated canine renal artery compared with those of nicorandil and cromakalim. KRN2391 (10(-8)-3 x 10(-5) M), nicorandil (10(-7)-3 x 10(-4) M) and cromakalim (10(-8)-3 x 10(-5) M) relaxed renal arteries contracted by 25 mM KCl in a concentration-dependent manner. KRN2391-induced relaxation was inhibited by methylene blue (10(-5) M) and glibenclamide (10(-6) M). Nicorandil-induced relaxation was inhibited by methylene blue, but not by glibenclamide. The concentration-relaxation curve for cromakalim displayed a rightward parallel shift in the presence of glibenclamide. In the control observation, KRN2391 and nicorandil also produced full relaxation, but cromakalim did not. The present results suggest that KRN2391 acts as both a nitrate and a potassium channel opener, and nicorandil acts only as a nitrate and only in canine renal artery.

摘要

在本研究中，我们将KRN2391（N-氰基-N'-（2-硝氧乙基）-3-吡啶甲脒单甲磺酸盐）与尼可地尔和克罗卡林进行比较，研究了其在离体犬肾动脉中的作用方式。KRN2391（10^(-8)-3×10^(-5)M）、尼可地尔（10^(-7)-3×10^(-4)M）和克罗卡林（10^(-8)-3×10^(-5)M）以浓度依赖性方式舒张由25mM氯化钾收缩的肾动脉。KRN2391诱导的舒张作用被亚甲蓝（10^(-5)M）和格列本脲（10^(-6)M）抑制。尼可地尔诱导的舒张作用被亚甲蓝抑制，但不被格列本脲抑制。在格列本脲存在的情况下，克罗卡林的浓度-舒张曲线呈现向右平行移动。在对照观察中，KRN2391和尼可地尔也产生完全舒张，但克罗卡林没有。目前的结果表明，KRN2391既作为硝酸盐又作为钾通道开放剂起作用，而尼可地尔仅作为硝酸盐起作用，且仅在犬肾动脉中起作用。