title: Role of endogenous nitric oxide in septic shock.
abstract: Nitric oxide synthesized by a constitutive enzyme is a widespread mediator of cell-cell and intracellular communication. This mediator provides a continuous vasodilator influence in the cardiovascular system, modifies the function of circulating cells, and acts as a neurotransmitter. After exposure to bacterial endotoxin or certain cytokines, expression of a second, inducible nitric oxide synthase occurs in a wide variety of tissues. This enzyme produces large amounts of nitric oxide for long periods and has been implicated in pathophysiologic changes seen in sepsis. In some cells, including macrophages, the nitric oxide synthesized by the inducible enzyme is toxic and appears to be an important mediator in host defense. Studies in animals and in vitro have demonstrated that nitric oxide released from inducible nitric oxide synthase in other tissues may cause profound vasodilation, damage to host cells, and cardiac dysfunction. The hypotension of endotoxin- or cytokine-induced shock can be reversed by inhibitors of nitric oxide synthase and these agents may provide a novel therapeutic approach to the treatment of severe septic shock. Preliminary studies in humans suggest that inhibition of nitric oxide synthase improves BP and stabilizes hemodynamics; effects on mortality rates remain to be determined.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Vallance
authors.forename: S
authors.initials: S
authors.lastname: Moncada
mesh_terms: D000818:Animals; D004285:Dogs; D006801:Humans; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D012772:Shock, Septic / Q000209:etiology / Q000503:physiopathology*
chemical_list: D009569:Nitric Oxide