EFFECTS OF 3 INHIBITORS OF NITRIC-OXIDE SYNTHASE ON HOST-RESISTANCE TO BACTERIAL-INFECTION

To examine the effects of three nitric oxide synthase inhibitors on su rvival in a murine sepsis model. Design: Prospective randomized experi mental trials. Setting: Prospective randomized experimental trials. Se tting: Laboratory. Subjects: Female Balb/c mice. Interventions: Escher ichia coli (10(8) colony-forming-units/body) were injected into the pe ritoneal cavities of Balb/c mice. N-G-nitro-L-arginine-methyl-ester, N -G-monomethyl-L-arginine, or N-iminoethyl-L-ornithine was given at var ious concentrations, intraperitoneally, one hour before bacterial chal lenge. Measurements: One hundred and fifteen animals were observed for survival. Results: These inhibitors provided the mice no protection f rom the bacterial challenge. Notably, pretreatment with N-G-nitro-L-ar ginine-Methyl-ester (100 mg/kg i.p.) actually reduced survival time af ter E. coli challenge. Conclusions: Inhibition of nitric oxide product ion improved neither the survival time nor rate in this murine sepsis model.