Effects of inorganic nitrite on cardiac and skeletal muscle: physiology, pharmacology and therapeutic potential
Plasma nitrite is derived both from oxidation of nitric oxide that diffuses lumenally and from reduction of dietary sources of nitrate. Originally considered a weak vasodilator, recent studies have shown that its vascular effects are markedly enhanced under hypoxic conditions. Nitrite has also been shown to have other effects including protection against ischaemia-reperfusion injury and, very recently, to increase metabolic efficiency in skeletal muscle. These effects are apparent at concentrations only slightly above those observed physiologically. We propose a series of studies that will investigate the mechanism of the increased metabolic efficiency in skeletal muscle and whether similar changes occur in cardiac muscle. Finally, we will assess whether these effects can be exploited clinically in three disorders associated with impaired skeletal and/or cardiac muscle energy generation - intermittent claudication, angina, and chronic heart failure.