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17β-雌二醇对人冠状动脉的体外非内皮依赖性舒张作用

Endothelium independent relaxation of human coronary arteries by 17 beta-oestradiol in vitro.

作者信息

Mügge A, Riedel M, Barton M, Kuhn M, Lichtlen P R

机构信息

Division of Cardiology, Hannover Medical School, Germany.

出版信息

Cardiovasc Res. 1993 Nov;27(11):1939-42. doi: 10.1093/cvr/27.11.1939.

DOI:10.1093/cvr/27.11.1939
PMID:8287400
Abstract

OBJECTIVE

There is accumulating evidence that oestrogen replacement therapy protects against the development of coronary atherosclerosis and myocardial infarction in postmenopausal women. The mechanism of this protective effect is uncertain. The aim of this study was to measure the effects of 17 beta-oestradiol on human epicardial coronary artery tone.

METHODS

Coronary artery rings were obtained from explanted hearts during cardiac transplantation. The rings were suspended in organ baths for isometric tension measurements. The rings were precontracted with prostaglandin F2 alpha, and were then exposed to either 17 beta-oestradiol (0.3 nM-3 microM) or solvent control (0.2% ethanol v/v). In some rings, cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate content were measured by radioimmunoassay.

RESULTS

17 beta-Oestradiol induced a significant relaxation [maximum effect: 84(SD 18)%]. The onset of the relaxant effect occurred within 5 min, and was maximal within 40 min. The relaxation in response to 3 microM 17 beta-oestradiol was of similar magnitude in rings with and without intact endothelium. The maximum relaxation induced by 3 microM 17 beta-oestradiol was greater in arteries from hearts obtained from women than in those obtained from men [-100.0(3.0)% v -77.5(17.6)%, respectively]. The exposure of rings to 3 microM 17 beta-oestradiol for 30 min resulted in a significant increase in both cyclic AMP and cyclic GMP content, by 88% and 182%, respectively.

CONCLUSIONS

17 beta-Oestradiol produced an endothelium independent relaxation of precontracted human coronary arteries in vitro, and this effect was associated with an increase in both cyclic AMP and the cyclic GMP content. This direct relaxant effect of oestrogens on coronary arteries may contribute to the beneficial effects of oestrogen replacement therapy in postmenopausal women.

摘要

目的

越来越多的证据表明,雌激素替代疗法可预防绝经后女性冠状动脉粥样硬化和心肌梗死的发生。这种保护作用的机制尚不确定。本研究的目的是测量17β-雌二醇对人冠状动脉张力的影响。

方法

冠状动脉环取自心脏移植手术中取出的心脏。将环悬挂在器官浴槽中进行等长张力测量。先用前列腺素F2α使环预收缩,然后将其暴露于17β-雌二醇(0.3 nM - 3 μM)或溶剂对照(0.2%乙醇,v/v)中。在一些环中,通过放射免疫分析法测量环磷酸腺苷和环磷酸鸟苷的含量。

结果

17β-雌二醇引起显著的舒张作用[最大效应:84(标准差18)%]。舒张作用在5分钟内开始,40分钟内达到最大。在有完整内皮和无完整内皮的环中,对3 μM 17β-雌二醇的舒张反应幅度相似。3 μM 17β-雌二醇诱导的最大舒张在取自女性心脏的动脉中比取自男性心脏的动脉中更大[分别为-100.0(3.0)%和-77.5(17.6)%]。将环暴露于3 μM 17β-雌二醇30分钟导致环磷酸腺苷和环磷酸鸟苷含量分别显著增加88%和182%。

结论

17β-雌二醇在体外对预收缩的人冠状动脉产生非内皮依赖性舒张作用,且这种作用与环磷酸腺苷和环磷酸鸟苷含量的增加有关。雌激素对冠状动脉的这种直接舒张作用可能有助于雌激素替代疗法对绝经后女性的有益作用。

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