Protective Role of Inhaled Nitric Oxide in Ischemia/Reperfusion and Endotoxin-Induced Inflammation

Abstract

Endogenous production of nitric oxide (NO) plays an important role in regulating vascular tone, platelet adhesion and aggregation, white cell adhesion to endothelial cells, and host defense against infection. Inhaled NO gas has been shown to be effective as a selective pulmonary vasodilator in animal models of pulmonary hypertension and in adult and infant patients with pulmonary hypertension. Inhaled NO decreases pulmonary arterial pressure and pulmonary vascular resistance and improves oxygenation. This principle has been used sucessfully to treat acute respiratory distress syndrome (ARDS), persistent pulmonary hypertension of the newborn, and pulmonary hypertension in patients undergoing cardiac surgery. These applications take advantage of the physiological effect of NO endogenously synthesized by the vascular endothelium from the amino acid L-arginine in response to stimuli such as the activation of muscarinic receptors by acetylcholine. NO diffuses from endothelium to vascular smooth muscle, where it acts as a signal-transducing factor which activates soluble guanylate cyclase in smooth muscle cells, leading to vascular relaxation.