Effects of thiazide diuretic on vascular eicosanoid system of spontaneously hypertensive rats.
Effects of thiazide diuretic on vascular eicosanoid system of spontaneously hypertensive rats.
复制标题
噻嗪类利尿剂对自发性高血压大鼠血管类二十烷酸系统的影响。
作者：
A. Numabe;Y. Uehara;N. Hirawa;S. Takada;S. Yagi
为了评估血管类花生酸系统在噻嗪类药物治疗中的作用，我们检测了三氯甲噻嗪治疗2周的自发性高血压大鼠（SHR）的主动脉类花生酸系统。噻嗪类药物治疗引起的血压降低与血管抑制剂前列环素（PGI 2）生成的显著减少相关，而硝苯地平和卡托普利治疗均未降低血管PGI 2生成。噻嗪类利尿剂直接降低培养的血管平滑肌细胞（VSMC）中的PGI 2合酶活性，从而减少VSMC和主动脉壁中PGI 2的产生。呋塞米或吲达帕胺均未观察到对血管PGI 2生成的直接抑制作用。因此，三氯甲噻嗪可减少血管PGI 2的生成，部分原因是其直接抑制PGI 2合酶;这可能与噻嗪类利尿剂对血管硬化改变的非有益作用有关。
To assess the role of the vascular eicosanoid system in thiazide therapy, we examined the aortic eicosanoid system of spontaneously hypertensive rats (SHR) treated with trichloromethiazide for 2 weeks. The blood pressure reduction caused by the thiazide treatment was associated with a significant decrease in vascular vasodepressor prostacyclin (PGI2) generation, whereas neither nifedipine nor captopril treatment lowered vascular PGI2 generation. The thiazide diuretic directly lowered PGI2 synthase activity in cultured vascular smooth muscle cells (VSMC), thereby decreasing PGI2 generation in the VSMC and probably in the aortic wall. This direct inhibitory effect on vascular PGI2 generation was not observed with either furosemide or indapamide. Thus, vascular PGI2 generation is reduced with trichloromethiazide, partly through its direct inhibition of PGI2 synthase; this has possible relevance to the non-beneficial effects of thiazide diuretics on the vascular sclerotic changes.