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.


METHODS
Prospective randomized experimental trials.


METHODS
Laboratory.


METHODS
Female Balb/c mice.


METHODS
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.


METHODS
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.
Fukatsu
K
K
Department of Surgery, University of Tokyo, Japan.
Saito
H
H
Fukushima
R
R
Lin
M T
MT
Inoue
T
T
Inaba
T
T
Furukawa
S
S
Han
I
I
Muto
T
T
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004927:Escherichia coli Infections / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009952:Ornithine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D011446:Prospective Studies; D011897:Random Allocation; D019323:omega-N-Methylarginine
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C065027:N(G)-iminoethylornithine; D001120:Arginine; D009952:Ornithine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester