KRN2391和尼可地尔在不同大小猪冠状动脉中的血管舒张机制。

Vasorelaxant mechanism of KRN2391 and nicorandil in porcine coronary arteries of different sizes.

作者信息

Miwa A, Kaneta S, Motoki K, Jinno Y, Kasai H, Okada Y, Fukushima H, Ogawa N

机构信息

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

出版信息

Br J Pharmacol. 1993 Jul;109(3):632-6. doi: 10.1111/j.1476-5381.1993.tb13619.x.

DOI:10.1111/j.1476-5381.1993.tb13619.x

PMID:8358563

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2175638/

Abstract

The relaxant mechanisms of action of KRN2391, a novel vasodilator, and nicorandil on epimyocardial coronary artery (2.5- 3.0 mm outer diameter) and mid-myocardial coronary artery (0.8-1.0 mm outer diameter) were investigated in porcine isolated coronary arteries. In addition, the vasorelaxant responses of KRN2391 and nicorandil were compared with those of nitroglycerin and cromakalim, a K+ channel opener, in epi- and mid-myocardial coronary arteries. 2. Nitroglycerin showed a more potent relaxant effect on epi-myocardial coronary arteries than on mid-myocardial coronary arteries, whereas cromakalim produced greater relaxation responses in mid-myocardial coronary arteries. There was no difference between epi- and mid-myocardial coronary arteries in terms of the relaxant effect of KRN2391 and nicorandil. 3. Relaxation induced by KRN2391 in epi- and mid-myocardial coronary arteries was inhibited by oxyhaemoglobin, a pharmacological antagonist of nitrovasodilators, and glibenclamide, a pharmacological antagonist of K+ channel opening drugs. However, the inhibitory effect of glibenclamide on KRN2391-induced relaxation was greater in mid-myocardial coronary artery than in epi-myocardial coronary artery. 4. Relaxation induced by nicorandil was inhibited by oxyhaemoglobin alone in epi-myocardial coronary arteries and by both oxyhaemoglobin and glibenclamide in mid-myocardial coronary arteries. 5. In epi- and mid-myocardial coronary arteries, relaxation induced by cromakalim was inhibited by glibenclamide but not by oxyhaemoglobin, whereas relaxation induced by nitroglycerin was inhibited by oxyhaemoglobin but not by glibenclamide. 6. These results suggest that KRN2391 and nicorandil exhibit a dual mechanism of action acting partly as a nitrate and partly as a K+ channel opener. The mechanism of action of these drugs depend on the segment of coronary artery studied. Furthermore, the dual mechanism of action of KRN2391 and nicorandil seems to contribute to the equipotent relaxant effect between epi- and mid-myocardial coronary arteries.

摘要

在猪离体冠状动脉中研究了新型血管扩张剂KRN2391和尼可地尔对心外膜冠状动脉（外径2.5 - 3.0毫米）和心肌中层冠状动脉（外径0.8 - 1.0毫米）的舒张作用机制。此外，还比较了KRN2391和尼可地尔与硝酸甘油和K⁺通道开放剂克罗卡林在心外膜和心肌中层冠状动脉中的血管舒张反应。2. 硝酸甘油对心外膜冠状动脉的舒张作用比对心肌中层冠状动脉更强，而克罗卡林在心肌中层冠状动脉中产生更大的舒张反应。KRN2391和尼可地尔在心外膜和心肌中层冠状动脉的舒张作用方面没有差异。3. KRN2391在心外膜和心肌中层冠状动脉中诱导的舒张受到硝基血管扩张剂的药理拮抗剂氧合血红蛋白和K⁺通道开放药物的药理拮抗剂格列本脲的抑制。然而，格列本脲对KRN2391诱导舒张的抑制作用在心肌中层冠状动脉中比在心外膜冠状动脉中更大。4. 尼可地尔在心外膜冠状动脉中诱导的舒张仅受到氧合血红蛋白的抑制，而在心肌中层冠状动脉中受到氧合血红蛋白和格列本脲两者的抑制。5. 在心外膜和心肌中层冠状动脉中，克罗卡林诱导的舒张受到格列本脲的抑制，但不受氧合血红蛋白的抑制，而硝酸甘油诱导的舒张受到氧合血红蛋白的抑制，但不受格列本脲的抑制。6. 这些结果表明，KRN2391和尼可地尔表现出双重作用机制，部分作用为硝酸盐，部分作用为K⁺通道开放剂。这些药物的作用机制取决于所研究的冠状动脉节段。此外，KRN2391和尼可地尔的双重作用机制似乎有助于心外膜和心肌中层冠状动脉之间等效的舒张作用。