The complex role of nitric oxide under physiologic versus septic conditions

versus septic conditions Physiology Nitric oxide (NO), a small endogenously produced molecule with a very short half-life, has been extensively characterized under physiologic and pathophysiologic conditions and also may represent a therapeutic target. NO synthesis via oxidation of L-arginine is catalyzed by diff erent NO synthases (NOSs). Within the three isoforms, the constitutively expressed neuronal NOS (nNOS) and endothelial NOS (eNOS) are regulated by calcium/calmodulin and post-translational modifi cations whereas the expression of inducible NOS (iNOS) is stimulated by pro-infl ammatory cytokines such as interferon-gamma or tumor necrosis factor-alpha. Released by endothelial cells, NO increases blood fl ow by relaxing vascular smooth muscle cells, modulating platelet aggregation and leukocyte-endothelial interactions [1], and reducing synthesis of pro-infl ammatory cytokines [2]. In addition, NO-derived radicals play an important role in the host immune defense against infections by killing phagocytosed microorganisms [3]. Apart from its enzymatic synthesis, NO can be released from S-nitrosohemoglobin with an increased effi ciency under conditions of low oxygen tension, explaining hypoxic vasodilation aimed at increasing regional blood fl ow [4]. In addition, the main reservoir for NO in human plasma is S-nitroso-serum albumin, which allows NOmediated regulation of vascular tone [5].