Inhibition of nitric oxide synthesis improves survival in a murine peritonitis model of sepsis that is not cured by antibiotics alone.
Inhibition of nitric oxide synthesis was investigated in a murine model of advanced sepsis in which antibiotic therapy alone did not improve survival. Seven hours after receiving a lethal intraperitoneal challenge with live Escherichia coli, mice were given either NG-monomethyl-L-arginine (L-NMMA) intravenously, imipenem-cilastatin subcutaneously or a combination of both. L-NMMA (3-300 mg/kg) or imipenem-cilastatin (10 or 50 mg/kg) given alone did not improve survival; co-administration of L-NMMA and either 10 or 50 mg imipenem-cilastatin/kg improved survival significantly. These findings suggest that nitric oxide contributes to the morbidity associated with advanced sepsis and that nitric oxide synthase inhibition may improve the efficacy of conventional antimicrobial treatment of severe infections.
Teale
D M
DM
ICI Pharmaceuticals, Macclesfield, Cheshire, UK.
Atkinson
A M
AM
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015377:Cilastatin / Q000627:therapeutic use*; D000077728:Cilastatin, Imipenem Drug Combination; D004195:Disease Models, Animal; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000378:metabolism; D015378:Imipenem / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase; D010538:Peritonitis / Q000188:drug therapy* / Q000378:metabolism; D019323:omega-N-Methylarginine
D004338:Drug Combinations; D015377:Cilastatin; D019323:omega-N-Methylarginine; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases