NOS2 deficiency increases intestinal metabolism both in nonstimulated and endotoxemic mice.

Abstract

Animal studies have suggested that nitric oxide (NO) synthases (NOS) play a role in the regulation of protein metabolism in endotoxemia. We therefore investigated the role of inducible NOS (NOS2) on intestinal protein and neuronal NOS (NOS1) and endothelial NOS (NOS3) on amino acid metabolism. Three groups of mice were studied: 1) wild-type (WT), 2) NOS2 knockout (NOS2-KO), and 3) NOS2-KO + N(omega)-nitro-l-arginine methyl ester (NOS2-KO + l-NAME), both in nonstimulated and LPS-treated conditions. By infusion of the stable isotopes l-[phenyl-(2)H(5)]Phe, l-[phenyl-(2)H(2)]Tyr, l-[guanidino-(15)N(2)]Arg, and l-[ureido-(13)C; (2)H(2)]citrulline (Cit), intestinal protein, amino acid, and Arg/NO metabolism were studied on the whole body level and across intestine. In nonstimulated situations, NOS2 deficiency increased whole body protein turnover and intestinal Gln uptake and Cit production. In NOS2-KO + l-NAME, the above-mentioned changes were reversed. After LPS in WT, whole body NO and Cit production increased. In contrast to this, LPS decreased net intestinal Gln uptake, whole body NO, and Cit production in NOS2-KO mice. Treatment of NOS2-KO + l-NAME with LPS was lethal in eight 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 the endotoxemic NOS2-KO + l-NAME group might play a role in mortality in that group.

• Authors: Yvonne L J Vissers, Marcella M Hallemeesch, Peter B Soeters, Wouter H Lamers, Nicolaas E P Deutz
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 286 Issue 5 Pg. G747-51 (May 2004) ISSN: 0193-1857 [Print] United States
• PMID: 14656712 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Lipopolysaccharides
• Proteins
• Glutamine
• Citrulline
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type I
• Nitric Oxide Synthase Type II
• Nitric Oxide Synthase Type III
• Nos1 protein, mouse
• Nos2 protein, mouse
• Nos3 protein, mouse
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Citrulline (metabolism)
• Endotoxemia (metabolism)
• Enzyme Inhibitors (pharmacology)
• Glutamine (metabolism)
• Intestinal Mucosa (metabolism)
• Intestines (drug effects)
• Lipopolysaccharides (pharmacology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide Synthase (deficiency, physiology)
• Nitric Oxide Synthase Type I
• Nitric Oxide Synthase Type II
• Nitric Oxide Synthase Type III
• Proteins (metabolism)