NITRIC-OXIDE IN CARDIOVASCULAR-DISEASES

Nitric oxide (NO), synthesized from L-arginine by a family of NO synth ases (NOS), is a widespread biological mediator implicated in many phy siological and pathophysiological processes, including a variety of ca rdiovascular diseases. Endothelium-derived NO, synthesized by a consti tutive NOS, is involved in hypertension, atherosclerosis and certain h eart diseases. In hypertension and arterosclerosis the role of NO is s till controversial and seems to vary depending on the stage of the dis ease and model studied. In spontaneous hypertension, the production of NO is increased, but inefficacious, probably because of increased ina ctivation. In salt-induced hypertension NO production may be impaired. In atherosclerosis, an enhanced degradation of NO by superoxide radic als may explain the reduced endothelium-dependent relaxations. In pulm onary hypertension, the use of NO gas inhalation has been proposed as a future therapy for this condition. In the heart, NO regulates corona ry flow and myocardial function; both functions are altered in coronar y artery disease and cardiomyopathy. Nitric oxide synthesized by the i nducible NOS takes part in several immunopathological diseases, such a s endotoxin shock, which can particularly affect the heart. In endotox aemia inducible NOS is overexpressed and the excess in NO production m ay 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 chara cteristic of this disease. Treatment with inhibitors of NO synthesis i s a promise for the future.