Inhibition by angiotensin converting enzyme inhibitors of endothelin secretion from cultured human endothelial cells.
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.
Yoshida
H
H
Second Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
Nakamura
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002478:Cells, Cultured; D016232:Endothelins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D007703:Peptidyl-Dipeptidase A / Q000494:pharmacology; D011863:Radioimmunoassay; D014471:Umbilical Veins
D000806:Angiotensin-Converting Enzyme Inhibitors; D016232:Endothelins; D007703:Peptidyl-Dipeptidase A