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Abstract

Nitric oxide biology has been extensively studied and several aspect of its roles in physiological and pathophysiology clarified. Nitric oxide exerts critical and diverse functions in the cardiovascular system. Impairment of NO production and/or function plays a key role in a number of cardiovascular disease processes, including atherosclerosis, thrombosis, restenosis, cerebral vasospasm and hypertension. Replacement of endogenous NO with exogenous drug-derived NO has been a common medical practice for many years, and these pharmacological compounds present an attractive option in the treatment of cardiovascular disease. Nitric oxide donors either donate NO directly or are pro-drugs that require enzymatic metabolism to generate bioactive NO. Direct NO donors such as organic nitrates have been used for many years in cardiovascular therapeutics but they exhibit limitations such as the development of nitrate tolerance and their inability to improve patient outcome among others. Cofactor-dependent and enzymatically active pro-drugs such as molsidomine, s-nitrosothiols, diazeniumdiolates and mesoionic oxatriazoles and bifunctional NO-donors such as NO-aspirin are potential alternatives to conventional nitrates. This review focuses on the chemical and pharmacological characteristics of conventional and novel NO donors, and their therapeutic potential in the treatment of a variety of cardiovascular disorders.