The role of nitric oxide and other endothelium-derived vasoactive substances in vascular disease.

Alteration in the release and action of endothelium-derived vasoactive factors is responsible for changes in vascular reactivity early in the course of vascular disease. These factors include nitric oxide, eicosanoids, endothelium-derived hyperpolarizing factor, endothelin, and angiotensin II. Because endothelial dysfunction occurs at early stages of disease, it may reflect physiological changes that, if allowed to become chronic, are responsible for changes in vascular structure and growth and adhesivity to platelets and leukocytes, ultimately leading to atherosclerosis and thrombosis. Each of the major risk factors predisposing to vascular disease are associated with endothelial cell dysfunction, suggesting a direct etiologic link between the effects of the risk factors on the endothelium and their propensity to accelerate vascular disease. Restoration or replacement of endothelium-derived factors such as nitric oxide and prostacyclin, which impede the progression of vascular disease, or preventing the action of mediators such as vasoconstrictor eicosanoids, angiotensin II, or endothelin, which accelerate the progression of vascular disease, has become a useful paradigm in the treatment and prevention of vascular disease. Thus, understanding the physiology of endothelium-derived vasoactive factors is a necessary part of every physician's education.