新型血管扩张剂Ki1769在离体大鼠主动脉中的特性

Characteristics of Ki1769, a novel vasodilator, in isolated rat aorta.

作者信息

Kashiwabara T, Nakajima T, Kasai H, Nakajima S, Izawa T, Ogawa N

机构信息

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

出版信息

Arch Int Pharmacodyn Ther. 1994 Mar-Apr;327(2):175-83.

PMID:7979826

Abstract

The vasorelaxant mechanism of a newly synthesized vasodilator, Ki1769 [N-cyano-N'-(2-phenethyl)-3-pyridinecarboximidamide], was studied in isolated rat aorta in comparison with cromakalim. Ki1769 (10(-8)-10(-5) M) and cromakalim (10(-8)-10(-5) M) produced a concentration-dependent relaxation and the EC50 values for Ki1769 and cromakalim were (8.60 +/- 1.90) x 10(-7) M and (1.36 +/- 0.18) x 10(-7) M, respectively. Ki1769- and cromakalim-induced relaxations were competitively antagonized by glibenclamide with pA2 values of 6.83 and 6.93, respectively. Charybdotoxin, apamine, atropine, propranolol and indomethacin did not affect the Ki1769-induced relaxation. An increase in 86Rb efflux was induced by Ki1769. Glibenclamide attenuated the increase in 86Rb efflux produced by Ki1769. These results suggest that the vasorelaxant effect of Ki1769 is based on the glibenclamide-sensitive K channel-opening action.

摘要

与克罗卡林相比，在离体大鼠主动脉中研究了新合成的血管舒张剂Ki1769 [N-氰基-N'-(2-苯乙基)-3-吡啶甲脒]的血管舒张机制。Ki1769（10^(-8)-10^(-5) M）和克罗卡林（10^(-8)-10^(-5) M）产生浓度依赖性舒张，Ki1769和克罗卡林的EC50值分别为(8.60±1.90)×10^(-7) M和(1.36±0.18)×10^(-7) M。格列本脲竞争性拮抗Ki1769和克罗卡林诱导的舒张，pA2值分别为6.83和6.93。大蝎毒素、蜂毒明肽、阿托品、普萘洛尔和吲哚美辛不影响Ki1769诱导的舒张。Ki1769诱导86Rb外流增加。格列本脲减弱了Ki1769引起的86Rb外流增加。这些结果表明，Ki1769的血管舒张作用基于格列本脲敏感的钾通道开放作用。