Nitric Oxide in Sepsis

Wray, Gillian M.; Thiemermann, Christoph

doi:10.1007/0-306-46816-6_13

Cited by 4 publications

(2 citation statements)

References 61 publications

(62 reference statements)

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“…Elevation of serum IFN-γ levels has also been described in iNOS −/ − mice infected with T. brucei or Leishmania major 3856. The discrepant findings in iNOS −/ − mice and animals administered iNOS inhibitors may reflect NOS-independent actions of inhibitors such as aminoguanidine 57, or residual or compensatory mechanisms in the mice 58. Our results indicate that NO· production plays an important antimicrobial effector role during salmonellosis.…”

Section: Discussionsupporting

confidence: 51%

Antimicrobial Actions of the Nadph Phagocyte Oxidase and Inducible Nitric Oxide Synthase in Experimental Salmonellosis. II. Effects on Microbial Proliferation and Host Survival in Vivo

Mastroeni

Vázquez‐Torres

Fang

et al. 2000

The Journal of Experimental Medicine

367

325

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The roles of the NADPH phagocyte oxidase (phox) and inducible nitric oxide synthase (iNOS) in host resistance to virulent Salmonella typhimurium were investigated in gp91phox −/−, iNOS −/−, and congenic wild-type mice. Although both gp91phox −/− and iNOS −/− mice demonstrated increased susceptibility to infection with S. typhimurium compared with wild-type mice, the kinetics of bacterial replication were dramatically different in the gp91phox −/− and iNOS −/− mouse strains. Greater bacterial numbers were present in the spleens and livers of gp91phox −/− mice compared with C57BL/6 controls as early as day 1 of infection, and all of the gp91phox −/− mice succumbed to infection within 5 d. In contrast, an increased bacterial burden was detected within reticuloendothelial organs of iNOS −/− mice only beyond the first week of infection. Influx of inflammatory CD11b+ cells, granuloma formation, and serum interferon γ levels were unimpaired in iNOS −/− mice, but the iNOS-deficient granulomas were unable to limit bacterial replication. The NADPH phagocye oxidase and iNOS are both required for host resistance to wild-type Salmonella, but appear to operate principally at different stages of infection.

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Section: Discussionsupporting

confidence: 51%

Antimicrobial Actions of the Nadph Phagocyte Oxidase and Inducible Nitric Oxide Synthase in Experimental Salmonellosis. II. Effects on Microbial Proliferation and Host Survival in Vivo

Mastroeni

Vázquez‐Torres

Fang

et al. 2000

The Journal of Experimental Medicine

367

325

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“…Induction of NOS-II is seen in models of septic shock, 45,46 whereas increased levels of nitrate as NO degradation product have been observed in animal models 47 and humans. 48,49 These might be related to NOS-II, as inhibitors (and dexamethasone) prevent hypotension and decrease in PO 2 , and the increase in nitrate levels following Escherichia coli lipopolysaccharide treatment in rats.…”

Section: Sepsismentioning

confidence: 98%

Biology and chemistry of the inhibition of nitric oxide synthases by pteridine‐derivatives as therapeutic agents

Matter¹,

Kotsonis²

2004

Medicinal Research Reviews

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Inhibitors of the family of nitric oxide synthases (NOS-I-III; EC 1.14.13.39) are of interest as pharmacological agents to modulate pathologically high nitric oxide (NO) levels in inflammation, sepsis, and stroke. In this article, we discuss the approach for targeting the unique (6R)-5,6,7,8-tetrahydro-L-biopterin (H4Bip) binding site of NOS by appropriate inhibitors. This binding site maximally increases enzyme activity and NO production from the substrate L-arginine upon cofactor binding. The first generation of H4Bip-based NOS inhibitors was based on 4-amino H4Bip derivatives in analogy to anti-folates such as methotrexate. In addition, we discuss the structure-activity relationship of a related series of 4-oxo-pteridine derivatives. Furthermore, molecular modeling studies provide an understanding of pterin antagonism on a structural level based on favorable and unfavorable interactions between protein binding site and ligands. These techniques include 3D-QSAR (CoMFA, CoMSIA) to understand ligand affinity and GRID/consensus principal component analysis (CPCA) to learn about selectivity requirements. Collectively these approaches, in combination with the presented SAR and structural data, provide useful information for the design of novel NOS inhibitors with increased isoform selectivity.

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Aerobic Gram-Positive Organisms

Besch‐Williford¹,

Franklin²

2007

The Mouse in Biomedical Research

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Nitric Oxide in Sepsis

Cited by 4 publications

References 61 publications

Antimicrobial Actions of the Nadph Phagocyte Oxidase and Inducible Nitric Oxide Synthase in Experimental Salmonellosis. II. Effects on Microbial Proliferation and Host Survival in Vivo

Antimicrobial Actions of the Nadph Phagocyte Oxidase and Inducible Nitric Oxide Synthase in Experimental Salmonellosis. II. Effects on Microbial Proliferation and Host Survival in Vivo

Biology and chemistry of the inhibition of nitric oxide synthases by pteridine‐derivatives as therapeutic agents

Aerobic Gram-Positive Organisms

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