Vascular endothelial cells play important roles in atherogenesis, and bradykinin is associated with atherosclerosis. The effect of bradykinin on apoptosis in human umbilical vein endothelial cells (HUVECs) was investigated, with a focus on Ca kinetics and nitric oxide production. In serum-free conditions, the number of apoptotic cells increased in a time-dependent manner, but this increase was inhibited by bradykinin in a dose-dependent manner. The apoptosis inhibited by bradykinin was reduced by nitric oxide inhibitor N -monomethyl- l -arginine ( l -NMMA) and consequently restored by combined treatment with l -NMMA and l -arginine. Bradykinin increased influx of extracellular Ca , generation of inositol 1,4,5-trisphosphate, and release of Ca from intracellular storage sites, thus increasing the total intracellular Ca concentration (Ca i). Bradykinin increased nitric oxide production, which was inhibited by l -NMMA and restored by combined treatment with l -NMMA and l -arginine. Sodium nitroprusside (SNP) dose-dependently increased nitric oxide production and inhibited apoptosis; however, 10 M SNP did not inhibit apoptosis. Caspase-3 inhibitor, acetyl-Asp-Met-Gln-Asp-aldehyde, enhanced bradykinin-induced inhibition of apoptosis but did not effect bradykinin-induced nitric oxide production. These findings suggest that bradykinin inhibits serum-depletion-induced apoptosis in HUVECs by enhancing nitric oxide production via an increase in Ca i.