ヒト培養血管内皮細胞のＰＧＩ２産生に及ぼすアンギオテンシン変換酵素関連物質の影響 単離血管との比較

Abstract

The effects of angiotensin I (AI)-converting enzyme (ACE) linked substances upon PGI2 generation were investigated using cultured human vascular endothelial cells and rat aortic rings.Endothelial cells were obtained from human umbilical cord vein and cultured by the modified method of Jaffe et al. PGI2 level was measured by radioimmunoassay of its stable metabolite 6-keto PGF1α, and ACE activity was assayed by Lieberman's method.In the endothelial cells, addition of AI or bradykinin (BK) enhanced PGI2 generation and also increased ACE activity in the culture medium, but angiotensin II (AII) did not show any effect. Captopril inhibited both of PGI2 generation and ACE activity in a dose dependent manner, but the enhancement of PGI2 generation by AI or BK was not affected by the pretreatment with captopril. Meanwhile in the rat aortic rings, AI, AII, and BK enhanced PGI2 generation but captopril decreased PGI2 generation in its higher concentration (10-3M), and at the same time mechanical stimulation enhanced PGI2 generation. But in the aortic rings whose endothelium was rubbed with blade, PGI2 generation and AII induced PGI2 enhancement remarkably decreased.Through these results it was suggested that conversion of AI to AII by ACE was suspected not to cause the enhancement of PGI2 generation in the endothelial cells, and that the enhanced PGI2 generation of aortic rings by AII was considered to be due to interaction of smooth muscle cells and endothelial cells. The previously reported hypothesis that captopril enhanced PGI2 generation by the accumulation of AI or BK via ACE inhibition, was not confirmed in this experimental system, and captopril was proved to inhibit PGI2 generation directly. It was rather suggested that the enhanced PGI2 generation in the endothelial cells by AI or BK was probably controlled by their ACE activation, as an autoregulation mechanism.