Document Detail

Therapeutic effects of imidazolineoxyl N-oxide against endotoxin shock through its direct nitric oxide-scavenging activity.
MedLine Citation:
PMID:  8048966     Owner:  NLM     Status:  MEDLINE    
We recently found a new class of nitric oxide (NO) antidote, i.e., 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide derivatives (PTIOs). It has a potent inhibitory action against endothelium-derived relaxing factor. Here, we report the effect of a water-soluble carboxy derivative of PTIO (carboxy-PTIO) on endotoxin shock. Endotoxin [lipopolysaccharide (LPS)] (10 mg/kg) was injected into Wistar rats, and the mean arterial blood pressure (MABP), heart rate and urinary parameters were continuously measured. The MABP and urine volume gradually decreased during 1 hr after LPS injection, and within 4 hr, both values decreased to 50-70%. When carboxy-PTIO at 0.056-1.70 mg/kg/min was infused for 1 hr beginning 90 min after the LPS injection, the hypotension, renal dysfunction and survival rate were much improved and the state of shock was avoided. Carboxy-PTIO administered to normal rats did not affect each parameter. Measurement of urinary output of carboxy-PTIO and carboxy-2-phenyl-4,4,5,5-tetramethylimidazole-1-oxyl (carboxy-PTI), which is a reaction product of carboxy-PTIO and NO, showed that conversion of carboxy-PTIO to carboxy-PTI was augmented by LPS treatment due to the increased production of NO, and that the enhanced conversion (PTIO-->PTI) was significantly inhibited by administration of N omega-monomethyl-L-arginine. This indicates that carboxy-PTIO exhibits a potent therapeutic value in endotoxin shock through the direct scavenging action against NO.
M Yoshida; T Akaike; Y Wada; K Sato; K Ikeda; S Ueda; H Maeda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  202     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  1994 Jul 
Date Detail:
Created Date:  1994-09-01     Completed Date:  1994-09-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  923-30     Citation Subset:  IM    
Department of Urology, Kumamoto University School of Medicine, Japan.
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MeSH Terms
Blood Pressure
Cyclic N-Oxides / therapeutic use*
Escherichia coli
Free Radical Scavengers*
Heart Rate
Imidazoles / therapeutic use*
Kidney / physiopathology
Nitric Oxide / metabolism*
Rats, Wistar
Shock, Septic / chemically induced,  drug therapy*,  physiopathology
Reg. No./Substance:
0/Benzoates; 0/Cyclic N-Oxides; 0/Free Radical Scavengers; 0/Imidazoles; 0/Lipopolysaccharides; 10102-43-9/Nitric Oxide; 145757-47-7/1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole

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