NITRIC-OXIDE - A PHYSIOLOGICAL MESSENGER

Purpose: To review the physiologic role of nitric oxide, an unusual me ssenger molecule that mediates blood vessel relaxation, neurotransmiss ion, and pathogen suppression. Data Sources: A MEDLINE search of artic les published from 1987 to 1993 that addressed nitric oxide and the en zyme that synthesizes it, nitric oxide synthase. Study Selection: Anim al and human studies were selected from 3044 articles to analyze the c linical importance of nitric oxide. Descriptions of the structure and function of nitric oxide synthase were selected to show how nitric oxi de acts as a biological messenger molecule. Data Extraction: Biochemic al and physiologic studies were analyzed if the same results were foun d by three or more independent observers. Data Synthesis: Two major cl asses of nitric oxide synthase enzymes produce nitric oxide. The const itutive isoforms found in endothelial cells and neurons release small amounts of nitric oxide for brief periods to signal adjacent cells, wh ereas the inducible isoform found in macrophages releases large amount s of nitric oxide continuously to eliminate bacteria and parasites. By diffusing into adjacent cells and binding to enzymes that contain iro n, nitric oxide plays many important physiologic roles. lt regulates b lood pressure, transmits signals between neurons, and suppresses patho gens. Excess amounts, however, can damage host cells, causing neurotox icity during strokes and causing the hypotension associated with sepsi s. Conclusions: Nitric oxide is a simple molecule with many physiologi c roles in the cardiovascular, neurologic, and immune systems. Althoug h the general principles of nitric oxide synthesis are known, further research is necessary to determine what role it plays in causing disea se.