Enhancement by captopril of bradykinin-induced calcium transients in cultured endothelial cells of the bovine aorta.
Using microscopic fluorometry and fura-2-loaded cultured bovine aortic endothelial cells, we determined the effects of captopril, an angiotensin converting enzyme (ACE) inhibitor, on bradykinin-induced Ca2+ transients in endothelial cells. In the presence of extracellular Ca2+, 10(-9) M bradykinin induced an early rise in the transients followed by sustained elevations of cytosolic calcium concentration ([Ca2+]i). Bradykinin concentration-dependently increased [Ca2+]i (EC50 6.7 x 10(-9) M). Captopril, 10(-5) M, enhanced and prolonged the bradykinin-induced Ca2+ transients and shifted the concentration-response curve to the left (EC50 8.5 x 10(-10) M). In porcine coronary aterial strips with intact endothelium, cumulative applications of bradykinin induced an endothelium-dependent relaxation during prostaglandin F2 alpha-induced contraction (EC50 = 2.0 x 10(-9) M). Treatment with 10(-5) M captopril enhanced the bradykinin-induced relaxation and shifted the concentration-response curve to the left (EC50 = 7.6 x 10(-10) M). Thus, captopril enhances the bradykinin-induced relaxation by mechanisms mainly dependent on the endothelium, namely the inhibition of ACE.
Hirano
K
K
Division of Molecular Cardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Hirano
M
M
Kanaide
H
H
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000502:physiology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016257:Fura-2; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013552:Swine
D002216:Captopril; D001920:Bradykinin; D002118:Calcium; D016257:Fura-2