Thirty Years of Saying NO

The historical demonstration by Furchgott and Zawadzki that removal of the endothelium abrogates the in vitro vasodilator effect of acetylcholine has led to the identification 30 years ago of nitric oxide (NO) as a major endogenous local regulator of vascular tone. When the ability of endothelial cells to produce NO is blunted, the ensuing vascular dysfunction sets the stage for the occurrence of cardiovascular disease in general, and atherosclerosis in particular. This review focuses, stepby-step, on the bioavailability (production, action, and disposition) of endothelium-derived NO as local regulator of vascular tone in health and disease. Obviously, there is much more than NO in the control of the degree of contraction of underlying vascular smooth muscle cells exerted by the endothelial cells. Indeed, they generate also prostacyclin and hyperpolarizing signals (initiating endothelium-dependent hyperpolarization [EDH] and thus relaxation) and produce vasoconstrictor mediators (endothelium-derived contracting factors and the peptide endothelin-1); those have been discussed elsewhere in detail.