肼屈嗪对猪冠状动脉内皮依赖性血管舒张作用的研究。

Studies on endothelium-dependent vasorelaxation by hydralazine in porcine coronary artery.

作者信息

Wei S, Kasuya Y, Yanagisawa M, Kimura S, Masaki T, Goto K

机构信息

Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.

出版信息

Eur J Pharmacol. 1997 Mar 5;321(3):307-14. doi: 10.1016/s0014-2999(96)00972-7.

DOI:10.1016/s0014-2999(96)00972-7

PMID:9085042

Abstract

Hydralazine relaxed porcine coronary artery strips in a concentration-dependent manner by distinct endothelium-dependent and endothelium-independent actions. With lower doses (< or = 10(-6) M), the hydralazine-induced relaxation appears to be completely endothelium-dependent and we designed the present study to elucidate the mechanisms of this endothelium-dependent relaxation. Hydralazine (10(-6) M)-induced endothelium-dependent relaxation was not affected by the presence of 10(-5) M indomethacin, 10(-3) M L-NG-nitro-arginine (L-NOARG) or 10(-5) M haemoglobin, and was accompanied by accumulation of cGMP but not of cAMP in artery strips. There was a close time-dependent parallel relationship between endothelium-dependent relaxation and accumulation of cGMP induced by hydralazine (10(-6) M). The endothelium-dependent relaxation and accumulation of cGMP induced by hydralazine showed much slower kinetics than those induced by ionomycin (10(-7) M). Pretreatment of the strips with actinomycin D (10 micrograms/ml) significantly inhibited not the endothelium-dependent relaxation and accumulation of cGMP induced by ionomycin (10(-7) M) but those induced by hydralazine (10(-6) M). These results suggest that hydralazine induces endothelium-dependent vasorelaxation via the slow accumulation of cGMP in the strips. This does not occur through the release of nitric oxide or prostaglandin I2 but through immediate transcription and probably expression of a molecule in the endothelium.

摘要

肼屈嗪通过不同的内皮依赖性和非内皮依赖性作用，以浓度依赖的方式舒张猪冠状动脉条。在较低剂量（≤10⁻⁶ M）时，肼屈嗪诱导的舒张似乎完全依赖内皮，我们设计了本研究以阐明这种内皮依赖性舒张的机制。10⁻⁶ M肼屈嗪诱导的内皮依赖性舒张不受10⁻⁵ M吲哚美辛、10⁻³ M L-硝基精氨酸（L-NOARG）或10⁻⁵ M血红蛋白的影响，并且在动脉条中伴随着cGMP而非cAMP的积累。肼屈嗪（10⁻⁶ M）诱导的内皮依赖性舒张与cGMP积累之间存在密切的时间依赖性平行关系。肼屈嗪诱导的内皮依赖性舒张和cGMP积累的动力学比离子霉素（10⁻⁷ M）诱导的要慢得多。用放线菌素D（10微克/毫升）预处理条带，显著抑制的不是离子霉素（10⁻⁷ M）诱导的内皮依赖性舒张和cGMP积累，而是肼屈嗪（10⁻⁶ M）诱导的。这些结果表明，肼屈嗪通过条带中cGMP的缓慢积累诱导内皮依赖性血管舒张。这不是通过一氧化氮或前列腺素I2的释放发生的，而是通过内皮中一种分子的即时转录和可能的表达发生的。