Effects of three inhibitors of nitric oxide synthase on host resistance to bacterial infection.

OBJECTIVE

To examine the effects of three nitric oxide synthase inhibitors on survival in a murine sepsis model.

DESIGN

Prospective randomized experimental trials.

SETTING

Laboratory.

SUBJECTS

Female Balb/c mice.

INTERVENTIONS

Escherichia coli (10(8) colony-forming-units/body) were injected into the peritoneal cavities of Balb/c mice. NG-nitro-L-arginine-methyl-ester, NG-monomethyl-L-arginine, or N-iminoethyl-L-ornithine was given at various concentrations, intraperitoneally, one hour before bacterial challenge.

MEASUREMENTS

One hundred and fifteen animals were observed for survival.

RESULTS

These inhibitors provided the mice no protection from the bacterial challenge. Notably, pretreatment with NG-nitro-L-arginine-methyl-ester (100 mg/kg i.p.) actually reduced survival time after E. coli challenge.

CONCLUSIONS

Inhibition of nitric oxide production improved neither the survival time nor rate in this murine sepsis model.