Stimulation of endothelial autacoid formation by inhibitors of angiotensin-converting enzyme.
We have investigated in human endothelial cells in culture the effects of angiotensin-converting enzyme (ACE) inhibitors on the concentration of intracellular free Ca2+ ([Ca2+]i) and the formation of nitric oxide (NO) and prostacyclin (PGI2). Enalaprilat, moexiprilat and ramiprilat similarly potentiated the increase in [Ca2+]i elicited by bradykinin and caused an increase in resting [Ca2+]i when given alone. The latter effect was long-lasting and accompanied by an increased formation of NO and PGI2. All of these effects were inhibited by the B2-kinin receptor antagonist Hoe 140, suggesting that the endogenous synthesis/release of bradykinin represents an autocrine mechanism for the stimulation of endothelial autacoid formation. Thus these findings strongly support the concept that ACE inhibitors promote local vasodilation by increasing the level of bradykinin generated in subthreshold concentrations by the endothelium.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D015773:Enalaprilat / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D017257:Ramipril / Q000031:analogs & derivatives / Q000494:pharmacology; D044005:Tetrahydroisoquinolines; D014471:Umbilical Veins
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C052549:ramiprilat; D011464:Epoprostenol; D007703:Peptidyl-Dipeptidase A; D015773:Enalaprilat; D006152:Cyclic GMP; D017257:Ramipril; D001920:Bradykinin; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine; C058302:moexipril