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硝基化合物在冠状动脉平滑肌中通过环鸟苷酸介导的舒张作用的证据。

Evidence for cyclic GMP-mediated relaxant effects of nitro-compounds in coronary smooth muscle.

作者信息

Kukovetz W R, Holzmann S, Wurm A, Pöch G

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1979 Dec;310(2):129-38. doi: 10.1007/BF00500277.

DOI:10.1007/BF00500277
PMID:231208
Abstract

The effects of the four nitro-compounds nitroglycerin, nitroprusside-Na, NaNO2 and B 744-99 were studied simultaneously on length and on cGMP-levels in isolated circular strips of bovine coronary arteries. 1. All 4 nitro-compounds concentration dependently relaxed the strips in close association with pronounced increases in cGMP-levels which preceded the mechanical responses. 2. The relaxant effects of all 4 nitro-compounds were significantly potentiated by the predominant inhibitor of cGMP-hydrolysis M & B 22,948, which also potentiated the increase in cGMP-levels of the two nitro-compounds in which it was studied (nitroglycerin and nitroprusside-Na). 3. Non-substituted cGMP and -- much stronger -- its 8 bromo-derivative also relaxed the strips and these effects were likewise potentiated by M & B 22,948. 4. When the log increase in cGMP produced by the 4 nitro-compounds were plotted against percent relaxation (probit scale) a linear and highly significant positive correlation was obtained. 5. The results provide evidence that the increases in cGMP caused by the 4 nitro-compounds studied are responsible for the smooth muscle relaxing actions of these drugs.

摘要

同时研究了四种硝基化合物硝酸甘油、硝普钠、亚硝酸钠和B 744 - 99对牛冠状动脉离体环行肌条长度和环鸟苷酸(cGMP)水平的影响。1. 所有四种硝基化合物均呈浓度依赖性地使肌条舒张,同时cGMP水平显著升高,且cGMP水平升高先于机械反应。2. 环鸟苷酸水解的主要抑制剂M & B 22,948能显著增强所有四种硝基化合物的舒张作用,它也增强了所研究的两种硝基化合物(硝酸甘油和硝普钠)的cGMP水平升高。3. 未取代的环鸟苷酸及其8 - 溴衍生物(作用更强)也能使肌条舒张,且这些作用同样被M & B 22,948增强。4. 当将四种硝基化合物产生的环鸟苷酸对数增加量与舒张百分比(概率尺度)作图时,得到了线性且高度显著的正相关。5. 结果表明,所研究的四种硝基化合物引起的环鸟苷酸增加是这些药物平滑肌舒张作用的原因。

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