Preserving vessel function during ischemic disease: new possibilities of inorganic nitrite therapy

Abstract

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the U.S. and through out the industrialized world. Moreover, the incidence of CVD is on the rise globally and continues to place a significant economic and sociological burden on humanity as a whole. There is no doubt that continued research into the pathophysiological mechanisms of CVD has made excellent strides in clinical diagnosis and management. However, significant limitations still exist with several aspects of CVD pathology namely our ability to protect and restore tissue function in response to acute or chronic ischemic events. Acute or chronic vessel occlusion contributes to nearly all forms of CVD and the ability to thwart these events along with restoration of ‘healthy’ vascular function are still lacking. What is more, a common underlying feature of cardiovascular disease is defective bioavailability of nitric oxide (NO) which serves broad physiological roles ranging from regulation of vascular reactivity and growth, inflammation, and thrombosis. Indeed, effective NO therapy has been considered by many to be the ‘holy grail’ for CVD intervention yet realization of this goal has remained elusive. Recent work from our laboratory and others have begun to identify straightforward yet novel approaches for selective NO therapy which involves chemical reduction of the inorganic nitrite anion (NO2−) back into bioavailable NO. While this may be a seemingly simplistic approach, inorganic nitrite therapy may hold significant potential as an effective and selective NO donor for acute and chronic ischemia secondary to cardiovascular disease.