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 × 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 × 10^-10 M). In porcine coronary aterial strips with intact endothelium, cumulative applications of bradykinin induced an endothelium-dependent relaxation during prostaglandin F_2α-induced contraction (EC₅₀ = 2.0 × 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 × 10^-10 M). Thus, captopril enhances the bradykinin-induced relaxation by mechanisms mainly dependent on the endothelium, namely the inhibition of ACE.