NOS2 deficiency increases intestinal metabolism both in non-stimulated and endotoxemic mice

Y.L.J. Vissers, M.M. Hallemeesch, P.B. Soeters, W.H. Lamers, N.E.P. Deutz

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

NOS2 deficiency increases intestinal metabolism both in non-stimulated and endotoxemic mice.

Vissers YL, Hallemeesch MM, Soeters PB, Lamers WH, Deutz NE.

Department of Surgery, Maastricht University, Maastricht, The Netherlands.

Animal studies have suggested that nitric oxide synthases (NOS) play a role in the regulation of protein metabolism in endotoxemia. We therefore investigated the role of NOS2 on one hand and NOS1 and NOS3 on the other hand on intestinal protein and amino acid metabolism. Three groups of mice were studied: (1) wildtypes (WT), (2) NOS2 knockouts (NOS2-KO), (3) NOS2-KO + N(omega)-nitro-L-arginine methyl ester (NAME), both in non-stimulated and lipopolysaccharide treated (LPS) conditions. By infusion of the stable isotopes L-[phenyl-(2)H5]phenylalanine, L-[phenyl-(2)H2]tyrosine, L-[guanidino-(15)N2]arginine and L-[ureido-(13)C; (2)H2]citrulline, whole-body and intestinal protein and amino acid and arginine/NO metabolism were studied. In non-stimulated situations, NOS2 deficiency increased whole-body protein turnover and intestinal glutamine uptake and citrulline production. In NOS2-KO+NAME, the above-mentioned changes were reversed. After LPS in WT, whole-body NO and citrulline production increased. In contrast to this, LPS decreased net intestinal glutamine uptake, whole-body NO and citrulline production in NOS2-KO. Treatment of NOS2-KO+NAME with LPS was lethal in eight out of eleven mice (73%). The surviving mice in this group showed a major drop in intestinal protein breakdown and synthesis to almost zero. Thus, both in baseline conditions and during endotoxemia, the absence of NOS2 upregulated NOS1 and/or NOS3, which increased intestinal metabolism. The drop in intestinal protein metabolism in endotoxemic NOS2-KO+NAME might play a role in the mortality in the endotoxemic NOS2-KO+NAME group
Original languageEnglish
Pages (from-to)G747-G751
JournalAmerican Journal of Physiology-Gastrointestinal and Liver Physiology
Volume286
Issue number5
DOIs
Publication statusPublished - 1 Jan 2004

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