Nitric oxide in health and disease – its role in the practice of medicine

Abstract

Nitric oxide (NO), originally discovered as an endothelium-derived relaxing factor, is now known to participate in the physiologic processes of the nervous, renal, gastrointestinal, and cardiovascular systems. NO is an important mediator of vasodilation and is a potent inhibitor of platelet aggregation and endothelial adhesion. Endothelial dysfunction, which is characterized by a deficit in endothelial NO, is associated with cardiovascular risk factors and is a harbinger of impending cardiovascular disease. The association of reduced NO and cardiovascular disease has led to research into drugs that might enhance the activity of endogenous NO or that can donate exogenous NO to vulnerable tissues. Drugs that donate NO include nitroglycerin, which has been used for more than 100 years in the management of angina pectoris. Drugs used to treat erectile dysfunction act primarily by inhibiting the degradation of the second messenger of NO, thus enhancing and prolonging its action. A novel approach to delivering exogenous NO is to link a NO-donating moiety to an existing drug to improve its safety profile. An example of this strategy is naproxcinod, which in clinical trials for osteoarthritis has demonstrated analgesic equivalence with the parent drug, naproxen, while attenuating some of the gastrointestinal and cardiovascular adverse effects. It is anticipated that the practice of medicine will continue to be affected as new drugs are developed that exploit the important pathways modulated by NO.