Nitric oxide production is stimulated by an increase of the concentration of cytosolic Ca(2+) in vascular endothelial cells. Recent evidence suggests that nitric oxide and cGMP might attenuate Ca(2+) influx and, at the same time, initiate a Ca(2+) removal mechanism, thereby decreasing the intracellular concentration of endothelial Ca(2+) in a negative feedback fashion. Such a negative feedback mechanism could serve to protect the endothelial cells from the detrimental effects of excessive nitric oxide and Ca(2+).