Since the discovery of an endothelium-derived relaxing factor (EDRF) by Furchgott and Zawadzki (Furchgott and Zawadzki, 1980), which was later identified as nitric oxide (NO) (Ignarro et al., 1987; Palmer el nl., 1987; Furchgott, 1988), it has become clear that there are a number of additional endothelium-derived vasodilator and vasoconstrictor autacoids (endothelin-1, prostaglandin H-2 and the endothelium-derived hyperpolarizing factor: EDHF). None of these autacoids play such a central role in the regulation of vascular tone and homeostasis as the primary EDRF, the free radical NO, which is generated via a five-electron oxidation of a guanidino nitrogen from L-arginine by an NO synthase (NOS). (C) 1999 Academic Press.