Urinary nitrate excretion in relation to murine macrophage activation. Influence of dietary L-arginine and oral NG-monomethyl-L-arginine
| Autor: | D L Granger, J B Hibbs, L M Broadnax |
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| Rok vydání: | 1991 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 146:1294-1302 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.146.4.1294 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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