Quantitative aspects of nitric oxide production in the heart.

Nitric oxide (NO) has essential roles in heart physiology, including the regulation of myocardial contractility and coronary blood flow, and in heart pathophysiology, particularly in the ischemic heart. NO is produced by both NO synthase (NOS)-dependent and NOS-independent pathways in the heart. This review summarizes quantitative aspects of NO production in the heart; the contribution of cardiomyocytes, endothelial cells (ECs), red blood cells (RBCs), and neurons are also discussed. Based on the available data, under normal conditions, the human heart produces about 50-70 µmol NO per day, primarily attributed to eNOS activity; ECs produce the highest amount of NO compared to other cell types in the heart. On the other hand, during ischemic conditions, NOS-independent NO production participates a significant role in the heart NO production that can exceed NOS-dependent NO generation. These data are relevant as most cardiovascular disorders are associated with NO dysfunction, and increasing NO bioavailability and signaling is a potential therapeutic approach for cardiovascular diseases.