Nitric oxide in the pathogenesis of sepsis.
In sepsis and septic shock, inflammatory mediators result in the production of increased concentrations of nitric oxide (NO) from the enzymatic breakdown of the amino acid L-arginine. The increased amounts of NO are responsible for changes in vasomotor tone, decreased vasopressor responsiveness, and decreased myocardial function, characteristic of septic insult. Therapeutic strategies designed to reduce the concentration of NO by inhibiting the action of the nitric oxide synthase enzyme, or by scavenging the excess NO, offer the potential to treat directly the vasomotor abnormalities and myocardial depression seen in sepsis and other inflammatory states. This article reviews the biology of NO in sepsis and discusses strategies for neutralization of the increased NO production, in the setting of severe sepsis and septic shock.
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Section of Critical Care Medicine, Rush Medical College and, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, USA.
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D000818:Animals; D002319:Cardiovascular System / Q000503:physiopathology; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology / Q000627:therapeutic use; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D018805:Sepsis / Q000188:drug therapy / Q000503:physiopathology*; D012772:Shock, Septic / Q000503:physiopathology; D019323:omega-N-Methylarginine / Q000494:pharmacology / Q000627:therapeutic use
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester