Exercise increases heart rate, and increased heart rate increases shear stress in all vascular beds. Metabolic vasodilation of the exercising skeletal muscle and myocardium increases blood flow, and increased blood flow increases shear stress in the respective conduit vessels. Elevated shear stress activates endothelial and red blood cell (RBC)-derived endothelial nitric oxide synthase (eNOS).

Nitrite is the main oxidation product of nitric oxide (NO) in plasma and sensitively reflects acute and chronic changes in eNOS activity. Nitrite oxidizes the heme-group of desoxyhemoglobin in RBC and desoxymyoglobin in vessels directly or via protonation and is then converted into NO. This reaction occurs along the physiological oxygen gradient and improves oxygen supply beyond blood flow supply. Apart from better blood flow and oxygen supply, NO also improves mitochondrial energy production in skeletal and cardiac muscle. All these mechanisms contribute to improved exercise performance.

Dietary intake of inorganic nitrate enhances performance in highly trained athletes, possibly through stepwise reduction of nitrate to nitrite and NO. Higher levels of plasma nitrite are associated with better exercise capacity in athletes.

Age-related endothelial dysfunction is associated with an impaired capacity to increase plasma nitrite in response to exercise, thus reflecting the lack of NO in the control of blood flow and oxygen supply.

Regular exercise is an established strategy in primary and secondary prevention of cardiovascular disease. To what extent such prevention is based on NO-related antagonism of atherosclerotic vascular remodelling and improved vasomotion is currently not clear.