Nitric Oxide was originally identified as a signal-transducing agent in vasodilation of endothelial vascular cells and underlying smooth muscle. A variety of signals that decrease blood pressure and inhibit platelet aggregation use nitric oxide as an intermediary. The nitric oxide synthase in endothelial vascular cells is acutely sensitive to calcium ion concentration; activation of the enzyme by Ca²⁺ causes nitric oxide accumulation. Because nitric oxide is a gas, it can diffuse rapidly into neighboring cells and control their metabolism, primarily by stimulating cGMP synthesis. Nitric oxide is unstable, with a chemical half-life of 1 to 5 seconds, so its actions are short-lived. Studies of intracellular localization of nitric oxide synthase and of nitric oxide synthase inhibitors have identified additional roles for nitric oxide as diverse as neurotransmission in the central nervous system and stimulation of erection of the penis.