ENDOGENOUS NITRIC-OXIDE IN CARDIOVASCULAR-DISEASE AND TRANSPLANTATION

Nitric oxide (NO), derived from the vascular endothelium and other cel ls of the cardiovascular system, has important roles in physiological regulation of blood flow and may have pathophysiological functions in cardiovascular disease. The mechanisms involved in NO-induced vasodila tion and cytotoxicity are briefly reviewed in the context of inflammat ory reactions and cardiovascular function. Although NO can hyperpolari ze vascular smooth muscle, activation of the endothelium can induce hy perpolarization and vasodilation by other means. Endogeneous inhibitor s of NO generated by leucocytes may compromise blood flow distribution after ischaemia and reperfusion injury. Chronic heart failure is asso ciated simultaneously with impairment of endothelium-dependent vasodil ation and with excess production of NO via the inducible NO synthase ( iNOS), although it is unclear whether the latter ameliorates or exacer bates ventricular dysfunction. Excess NO production is also one of the earliest signs of transplant rejection, and suppression of iNOS expre ssion by immuno-suppressant drugs such as cyclosporin A might be one m eans by which these drugs protect allografts. Disturbances in the acti vity of NOS isoforms in the artery wall also accompany the development of atherosclerosis, providing conditions propitious for vasospasm and thrombosis. Reversing the NO defects with therapeutic agents, includi ng angiotensin converting enzyme (ACE) inhibitors, offers promise in p rotecting against some manifestations of vascular disease.