Myoglobin’s novel role in nitrite-induced hypoxic vasodilation

Hypoxic vasodilation represents a key physiological response of the cardiovascular system to low tissue oxygen tension, adjusting local blood flow to meet the metabolic requirements in tissue. Vasodilation occurs by nitric oxide (NO) activation of the cyclic guanosine monophosphate (cGMP) signaling pathway in vascular smooth muscle cells. Under normoxia, NO is formed by the well-known endothelial NO synthase (eNOS) system while under hypoxia NO is generated from nitrite. We have unraveled the heme-protein myoglobin in vascular smooth muscle cells as a major source of NO generation by reduction of endogenous nitrite under hypoxia. This mediates hypoxic vasodilation under physiological conditions without direct involvement of eNOS and independently of effects on cardiac function.