Nitric oxide (NO), synthesized from L-arginine by a family of NO synthases (NOS), is a widespread biological mediator implicated in many physiological and pathophysiological processes, including a variety of cardiovascular diseases. Endothelium-derived NO, synthesized by a constitutive NOS, is involved in hypertension, atherosclerosis and certain heart diseases. In hypertension and arterosclerosis the role of NO is still controversial and seems to vary depending on the stage of the disease and model studied. In spontaneous hypertension, the production of NO is increased, but inefficacious, probably because of increased inactivation. In salt-induced hypertension NO production may be impaired. In atherosclerosis, an enhanced degradation of NO by superoxide radicals may explain the reduced endothelium-dependent relaxations. In pulmonary hypertension, the use of NO gas inhalation has been proposed as a future therapy for this condition. In the heart, NO regulates coronary flow and myocardial function; both functions are altered in coronary artery disease and cardiomyopathy. Nitric oxide synthesized by the inducible NOS takes part in several immunopathological diseases, such as endotoxin shock, which can particularly affect the heart. In endotoxaemia inducible NOS is overexpressed and the excess in NO production may account for the impaired cardiac performance of this condition. The overproduction of NO occurring in endotoxin shock is also responsible for the hypotension, catecholamine resistance and tissue damage characteristic of this disease. Treatment with inhibitors of NO synthesis is a promise for the future.
