title: N(omega)-nitro-L-arginine methyl ester effects on neutrophil function and bacterial clearance.
abstract: Nitric oxide synthase (NOS) inhibitors are considered promising as a therapeutic option in severe septic shock. The aim of this study was to investigate the effects of N-nitro-L-arginine methyl ester (L-NAME) application on neutrophil (PMN) respiratory burst, phagocytosis, and elimination of Escherichia coli from blood and tissue in rabbits. Twenty-eight female chinchilla rabbits were randomized to a treatment and control group. To quantify the bacterial clearance process, 10 colony forming units (CFU) of E. coli were injected intravenously into anesthetized rabbits. Animals in the L-NAME group had a significantly higher mortality compared with controls. NOS inhibition resulted in a significant delay of bacterial clearance (P < 0.001). These findings correlated with a significant augmentation of all organ E. coli findings (P = 0.002-0.035). PMN phagocytosis activity was notably reduced by L-NAME treatment during the experimental observation. Neutrophil burst, on the other hand, was amplified by NOS inhibition (P = 0.008). Our findings point to an interference with the PMN-dependent immune mechanisms after L-NAME treatment. The augmented PMN burst reaction could be a compensatory mechanism, potentially leading to tissue damage. Therefore, in this model, we find sufficient evidence pointing to a possible cause for the deleterious effect of early nonselective NOS inhibition in critically ill patients.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Dresden, Germany.
authors.forename: Sebastian N
authors.initials: SN
authors.lastname: Stehr
authors.forename: Sören
authors.initials: S
authors.lastname: Weber
authors.forename: Susanne C
authors.initials: SC
authors.lastname: Heller
authors.forename: Jutta
authors.initials: J
authors.lastname: Weikel
authors.forename: Matthias
authors.initials: M
authors.lastname: Hübler
authors.forename: Thea
authors.initials: T
authors.lastname: Koch
authors.forename: Axel R
authors.initials: AR
authors.lastname: Heller
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002682:Chinchilla; D004731:Endotoxins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000378:metabolism; D004927:Escherichia coli Infections / Q000188:drug therapy*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009924:Organ Culture Techniques; D010587:Phagocytosis; D010641:Phenotype; D011817:Rabbits; D013234:Stem Cells; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D004731:Endotoxins; D004791:Enzyme Inhibitors; D007773:Lactates; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester