Nitric Oxide-Induced Intracellular Ca2+ Modulation in Macrovascular Endothelial Cells

Background and Objectives:Nitric oxide (NO) reduces the intracellular Ca concentration ([Ca]i) in smooth muscle cells, whereas the effect of NO on [Ca]i in endothelial cells is still controversial. Therefore, the effect of NO on the [Ca]i, and its mechanism in mouse aortic endothelial cells (MAEC) and human umbilical vein endothelial cells (HUVEC) were examined. Materials and Methods:In primary cultured MAEC and HUVEC, cells were loaded with fura 2-AM and [Ca]i and measured using a microfluorometer. Results:The NO donor, sodium nitroprusside (SNP), reduced the [Ca]i in 72% of the cells tested (n=100). In the remaining cells, the effect of SNP was biphasic, or the [Ca]i was increased. In addition, the membrane-permeable cGMP, 8-bromo cGMP, decreased the [Ca]i. The effects of SNP and 8-bromo cGMP were inhibited by the soluble guanylate cyclase inhibitor, 1H-[1,2,4] oxadiazole[4,3-a]quinoxalin-1-one (ODQ), and the cGMP-dependent protein kinase inhibitor, KT5823, respectively. In contrast, in the presence of 8-bromo cGMP or ODQ, SNP increased the [Ca]i. Conclusion:These results suggest that NO inhibits the [Ca ]i through a cGMPdependent mechanism and increases the [Ca]i through a cGMP-independent mechanism. (Korean Circulation J 2004;34(6):600-609)