Clinical translation of nitrite therapy for cardiovascular diseases

The anion nitrite is an oxidative breakdown product of nitric oxide (NO) that has traditionally been viewed as a diagnostic marker of NO formation in biological systems. In this regard, nitrite has long been considered an inert oxidation product of NO metabolism. More recently, this view has changed with the discovery that nitrite represents a physiologically relevant storage reservoir of NO in blood and tissues that can readily be reduced to NO under pathological conditions. This has sparked a renewed interest in the biological role of nitrite and has led to an extensive amount of work investigating its therapeutic potential. As a result, nitrite therapy has now been shown to be cytoprotective in numerous animal models of disease. Given the very robust preclinical data regarding the cytoprotective effects of nitrite therapy it is very logical to consider the clinical translation of nitrite-based therapies. This article will review some of this preclinical data and will discuss the potential use of nitrite therapy as a therapeutic agent for the treatment of cardiovascular diseases including: ischemia-reperfusion injury (i.e. acute myocardial infarction and stroke), hypertension, angiogenesis, and as an adjunctive therapy for transplantation of various organs (i.e. liver and lung). (C) 2009 Elsevier Inc. All rights reserved.