Effects of nitric oxide synthase inhibitors on murine infection with Mycobacterium tuberculosis.
We have recently demonstrated that the macrophage L-arginine-dependent cytotoxic pathway effectively kills the virulent Erdman strain of Mycobacterium tuberculosis in vitro via the generation of toxic reactive nitrogen intermediates by the enzyme nitric oxide synthase. This report demonstrates that two distinct inhibitors of nitric oxide synthase (aminoguanidine and NG-monomethyl-L-arginine) render similar deleterious effects on tuberculous infection in mice, as assessed by mortality, bacterial burden, and pathological tissue damage, thus confirming the importance of reactive nitrogen intermediates in resistance against M. tuberculosis.
Chan
J
J
Departments of Medicine, Albert Einstein College of Medicine, Bronx, New York.
Tanaka
K
K
Carroll
D
D
Flynn
J
J
Bloom
B R
BR
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D014376:Tuberculosis / Q000201:enzymology / Q000382:microbiology* / Q000473:pathology; D019323:omega-N-Methylarginine
D006146:Guanidines; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C004479:pimagedine