Yoshida H, Nakamura M
Second Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
Life Sci. 1992;50(22):PL195-200. doi: 10.1016/0024-3205(92)90432-o.
We conducted a study to determine whether angiotensin converting enzyme inhibitors (ACEIs) inhibit endothelin secretion from cultured human endothelial cells. Confluent umbilical vein endothelial cells were incubated in multi-well plates with culture medium containing either captopril (10(-6), 10(-5), 10(-4) M) or enalaprilat (10(-7), 10(-6), 10(-5) M) for 6 hours. Immunoreactive endothelin in the medium was measured by radioimmunoassay. Calf serum (CS) stimulated endothelin release in a concentration-dependent manner, and both ACEIs inhibited 5% CS-stimulated endothelin release in a concentration-dependent manner. To explore the mechanisms of ACEI-induced suppression of endothelin release, the effects of angiotensin II (10(-8), 10(-7), 10(-6) M), angiotensin converting enzyme (0.1, 1, 10 mU/ml), bradykinin (10(-8), 10(-7), 10(-6) M), and sodium nitroprusside (10(-6), 10(-5), 10(-4) M) on endothelin release were also examined. Although angiotensin II and angiotensin converting enzyme had no significant effect on endothelin release, concentration-dependent suppression occurred with bradykinin and sodium nitroprusside. These results indicate that ACEIs inhibit the stimulated release of endothelin from human endothelial cells, and provide indirect evidence that ACEI-induced ET suppression may be mediated via potentiation of autacoid formation from the cells.
我们进行了一项研究，以确定血管紧张素转换酶抑制剂（ACEI）是否能抑制培养的人内皮细胞分泌内皮素。将汇合的脐静脉内皮细胞接种于多孔板中，分别用含有卡托普利（10^(-6)、10^(-5)、10^(-4)M）或依那普利拉（10^(-7)、10^(-6)、10^(-5)M）的培养基孵育6小时。采用放射免疫分析法测定培养基中免疫反应性内皮素。小牛血清（CS）以浓度依赖性方式刺激内皮素释放，两种ACEI均以浓度依赖性方式抑制5%CS刺激的内皮素释放。为了探讨ACEI抑制内皮素释放的机制，还研究了血管紧张素II（10^(-8)、10^(-7)、10^(-6)M）、血管紧张素转换酶（0.1、1、10mU/ml）、缓激肽（10^(-8)、10^(-7)、10^(-6)M）和硝普钠（10^(-6)、10^(-5)、10^(-4)M）对内皮素释放的影响。虽然血管紧张素II和血管紧张素转换酶对内皮素释放无显著影响，但缓激肽和硝普钠可产生浓度依赖性抑制。这些结果表明，ACEI可抑制人内皮细胞刺激的内皮素释放，并间接证明ACEI诱导的内皮素抑制可能是通过增强细胞自分泌物质的形成来介导的。
