title: [Nitric oxide--an important mediator in sepsis?].
abstract: Animal experiments suggest that hyperproduction of nitric oxide (NO) by the inducible isoform of the enzyme NO synthase (iNOS) may contribute to hypotension, cardiodepression and vascular hyporeactivity in septic shock. Lipopolysaccarides and cytokines, like tumor necrosis factor, interleukin-1 and interferon-gamma, have been shown to induce iNOS in the endothelium, vascular smooth muscle cells, macrophages and different parenchymal cells. In several animal models of septic shock, treatment with inhibitors of NO synthesis has been shown to improve haemodynamic variables and survival. In human septic shock, inhibition of NO synthesis has been shown to alter haemodynamic variables in short term studies. However, a large multicentre study was recently stopped due to increased mortality in patients in septic shock treated with the NO synthase inhibitor NG-monomethyl-L-arginine. The aim of this review is to discuss the role of NO in sepsis and the potential therapeutic implications of NO as a target in treatment of human septic shock. We emphasize that many septic patients have preexisting endothelial dysfunction or lung diseases, which may predispose to severe adverse effects during systemic inhibition of NO synthesis. We also focus on the lack of direct evidence for iNOS expression in human septic shock and on the discrepancy between animal and human data.
authors.affiliation: Anestesiavdelingen, Ullevål sykehus, Oslo.
authors.forename: K A
authors.initials: KA
authors.lastname: Kirkebøen
authors.forename: O A
authors.initials: OA
authors.lastname: Strand
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D004790:Enzyme Induction; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D012772:Shock, Septic / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D009569:Nitric Oxide; D019001:Nitric Oxide Synthase