Urinary nitrate excretion in relation to murine macrophage activation. Influence of dietary L-arginine and oral NG-monomethyl-L-arginine.
Murine macrophage oxidation of L-arginine guanidino nitrogen to nitrite/nitrate yields an intermediate effector, possibly nitric oxide, with antimicrobial activity. Total body nitrogen oxidation metabolism (NOM) was measured in vivo by determining the urinary nitrate excretion of mice ingesting a chemically defined nitrite/nitrate-free diet. As reported previously, mycobacterial infection with bacillus Calmétte-Guerin led to a large increase in urinary nitrate excretion. This increase was temporally related to macrophage activation in vivo. The substrate for macrophage nitrogen oxidation metabolism in vitro, L-arginine, was deleted from the diet without ameliorating the urinary nitrate excretion response induced by BCG. This suggested that L-arginine was synthesized endogenously because there are no other known natural substrates for NOM. A competitive inhibitor of NOM, the L-arginine analog, NG-monomethyl-L-arginine was fed to mice in their drinking water. NG-monomethyl-L-arginine ingestion blocked both basal and bacillus Calmétte-Guerin-induced urinary nitrate excretion over a 2-4 week time span. These experimental conditions should prove useful for further investigation on the role of macrophage NOM in host defense against intracellular microorganisms.
Granger
D L
DL
Division of Infectious Diseases, Duke University School of Medicine, Durham, NC 27710.
Hibbs
J B
JB
Broadnax
L M
LM
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D004032:Diet; D007113:Immunity, Innate / Q000502:physiology; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009163:Mycobacterium bovis / Q000276:immunology; D009566:Nitrates / Q000652:urine*; D009584:Nitrogen / Q000378:metabolism*; D010084:Oxidation-Reduction; D013997:Time Factors; D014376:Tuberculosis / Q000378:metabolism; D019323:omega-N-Methylarginine
D009566:Nitrates; D019323:omega-N-Methylarginine; D001120:Arginine; D009584:Nitrogen