Nonselective versus selective inhibition of inducible nitric oxide synthase in experimental endotoxic shock

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Serval ID
serval:BIB_A8CE9B40CA50
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Nonselective versus selective inhibition of inducible nitric oxide synthase in experimental endotoxic shock
Journal
Journal of Infectious Diseases
Author(s)
Liaudet  L., Rosselet  A., Schaller  M. D., Markert  M., Perret  C., Feihl  F.
ISSN
0022-1899 (Print)
Publication state
Published
Issued date
01/1998
Volume
177
Number
1
Pages
127-32
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan
Abstract
The effects of two nitric oxide synthase (NOS) inhibitors with different isoform selectivity were compared in a murine model of endotoxemia. Mice challenged with 70 mg/kg intraperitoneal (ip) lipopolysaccharide (LPS) were treated 6 h after LPS with either NG-gamma-L-arginine methyl ester (L-NAME, nonselective NOS inhibitor, 10-60 mg/kg), L-canavanine (selective inhibitor of inducible NOS, 50-300 mg/kg), or saline (0.2 mL) given ip. In a subset of mice, plasma concentrations of nitrate (NO breakdown product), lipase (pancreas injury), lactate dehydrogenase, and transaminases (liver injury) were measured 16 h after LPS. Although both inhibitors reduced plasma nitrate, they produced contrasting effects on survival and organ injury. L-NAME enhanced liver damage and tended to accelerate the time of death, while L-canavanine significantly reduced mortality and had no deleterious effects in terms of organ damage. These results indicate that nonselective NOS inhibitors are detrimental in endotoxic shock and support the potential usefulness of selective inducible NOS inhibitors in this setting.
Keywords
Animals Canavanine/administration & dosage/adverse effects/*therapeutic use Enzyme Inhibitors/administration & dosage/adverse effects/*therapeutic use Female L-Lactate Dehydrogenase/analysis/blood Lipase/analysis/blood Lipopolysaccharides/administration & dosage/pharmacology Liver/pathology Mice NG-Nitroarginine Methyl Ester/administration & dosage/adverse effects/*therapeutic use Nitrates/analysis/blood Nitric Oxide/metabolism Nitric Oxide Synthase/*metabolism Shock, Septic/*drug therapy/*metabolism Transaminases/analysis/blood
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 10:37
Last modification date
25/09/2019 7:10
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