Cytosolic Ca2+ transients in endothelium-dependent relaxation of pig coronary artery, and effects of captopril.
To determine the mechanism of endothelium-dependent relaxation by bradykinin, we simultaneously measured changes in cytosolic calcium concentrations ([Ca2+]i) and force of fura-2-loaded strips of porcine coronary artery. We also examined effects of captopril, an angiotensin converting enzyme inhibitor, on bradykinin-induced relaxation. Bradykinin, in a concentration-dependent manner (10(-10) to 10(-7) M), decreased both [Ca2+]i and force to resting levels, during 10(-5) M prostaglandin F2 alpha-induced contractions, only when endothelium was intact. Treatment with 10(-5) M captopril enhanced the bradykinin-induced decreases in [Ca2+]i and force and shifted the concentration-response curve to the left. During 118 mM K+ depolarization, bradykinin induced a greater relaxation than that expected from the reduction in [Ca2+]i. Captopril had no effects on the relationship between reduction in [Ca2+]i and relaxation induced by bradykinin. Bradykinin relaxes porcine coronary artery in an endothelium-dependent manner, by decreasing [Ca2+]i and also by controlling the Ca2+ sensitivity of the contractile apparatus of smooth muscle. Captopril enhanced the bradykinin-induced relaxation, with no apparent direct effect on Ca2+ sensitivity of the contractile apparatus.
Hirano
K
K
Division of Molecular Cardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kanaide
H
H
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D016257:Fura-2; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013552:Swine
D002216:Captopril; D015237:Dinoprost; D005996:Nitroglycerin; D001920:Bradykinin; D002118:Calcium; D016257:Fura-2