一些有机硝基酯诱导的血管平滑肌松弛与环GMP增加的关系。

K L Axelsson, R G Andersson, J E Wikberg
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引用次数: 27

摘要

研究了三种硝基化合物单硝酸甘油(GMN)、硝酸甘油(GDN)和硝酸乙二醇(EGDN)对组胺收缩的牛肠系膜动脉的作用。GDN和EGDN引起剂量依赖性松弛,并伴有内源性cGMP水平升高。GDN和EGDN的松弛作用ed50值分别为1.06 × 10(-6) M和4.20 × 10(-8) M。GMN作为松弛剂几乎完全无效,也没有引起cGMP的显著变化。回归分析显示GDN和EGDN松弛与cGMP升高之间存在显著相关性。加入cGMP变化的平方可以显著改善EGDN的回归模型,表明两者之间存在非线性关系。GDN松弛与cGMP增加呈双曲线关系。当cAMP的变化被包括在内时,EGDN的回归模型略有改进。对于GMN和GDN,加入cAMP的变化后,回归模型并没有得到改善。本研究为cGMP作为硝基化合物诱导血管平滑肌松弛的介质提供了进一步的证据。
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Correlation between vascular smooth muscle relaxation and increase in cyclic GMP induced by some organic nitro esters.

Three different nitro compounds glyceryl mononitrate (GMN), glyceryl dinitrate (GDN) and ethylene glycol dinitrate (EGDN) were tested on histamine contracted bovine mesenteric artery. GDN and EGDN caused a dose-dependent relaxation which was accompanied by an increase in the endogenous cGMP level. The ED50-value for GDN and EGDN with regard to the relaxant action was 1.06 X 10(-6) M and 4.20 X 10(-8), respectively. GMN was almost completely ineffective as a relaxing agent and did not cause any significant change in cGMP. Regression analysis revealed a significant correlation between relaxation and increase in cGMP for both GDN and EGDN. The regression model for EGDN could be significantly improved by including the squared cGMP change, indicating a non-linear relationship. With regard to GDN a hyperbolic relationship between relaxation and cGMP increase was found. A slight improvement of the regression model was found for EGDN when the change in cAMP was included. For GMN and GDN no improvement of the regression model could be revealed by including the change of cAMP. It is suggested that the present data give further evidence for cGMP as a mediator of vascular smooth muscle relaxation induced by nitro compounds.

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