title: Role of nitric oxide in shock: the large animal perspective.
abstract: Excessive nitric oxide (NO) formation plays important roles in the pathogenesis of shock and multiple organ failure in sepsis and acute lung injury (ALI). Evidence from studies in large animal models of shock provide further insight into the role of NO and the varying nitric oxide synthase (NOS) isoforms. Nonselective NOS inhibition in sepsis models reversed sepsis-induced derangements in hemodynamic status, but was associated with side effects such as pulmonary vasoconstriction and decreases in global oxygen delivery. Results from studies on specific inhibition of inducible NOS (iNOS, NOS-2) and neuronal NOS (nNOS, NOS-1) in sepsis models remain inconclusive, but suggest that both isoenzymes are involved in the pathophysiological processes. While the long-term effects of NOS inhibition in models of burn and inhalation injury remain unknown, specific iNOS inhibition attenuated ALI without worsening injury-related pulmonary hypertension. Further investigation in large animal models is warranted to clarify the time course of increased expression and/or activity of different NOS isoenzymes and the effects of specific inhibition of the NOS isoforms at different time points.
authors.affiliation: Investigational Intensive Care Unit, University of Texas Medical Branch, 610 Texas Avenue, Galveston, Texas 77550, USA. lanm@gmx.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Lange
authors.forename: Perenlei
authors.initials: P
authors.lastname: Enkhbaatar
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Nakano
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Traber
mesh_terms: D000818:Animals; D002056:Burns / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D019446:Endotoxemia / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology*; D012756:Sheep; D012772:Shock, Septic / Q000503:physiopathology*; D013552:Swine
chemical_list: D009569:Nitric Oxide