Related Experiment Video
Updated: Aug 29, 2026
Functional Assessment of Intestinal Motility and Gut Wall Inflammation in Rodents: Analyses in a Standardized Model of Intestinal Manipulation
Published on: September 11, 2012
NOS2 deficiency increases intestinal metabolism both in nonstimulated and endotoxemic mice
Yvonne L J Vissers1, Marcella M Hallemeesch, Peter B Soeters
1Dept. of Surgery, Maastricht Univ., PO Box 616, NL-6200 MD Maastricht, The Netherlands.
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.
Insights
Nitric oxide synthase 2 (NOS2) deficiency alters protein and amino acid metabolism. Its absence upregulates other NOS enzymes, impacting intestinal function and survival during endotoxemia.
Area of Science:
- Physiology
- Biochemistry
- Immunology
Background:
- Nitric oxide synthases (NOS) are implicated in regulating protein metabolism during endotoxemia.
- The specific roles of inducible NOS (NOS2), neuronal NOS (NOS1), and endothelial NOS (NOS3) in intestinal metabolism require further elucidation.
Purpose of the Study:
- To investigate the role of NOS2 in intestinal protein and amino acid metabolism.
- To examine the influence of NOS1 and NOS3 in the absence of NOS2 during both basal and endotoxemic conditions.
Main Methods:
- Utilized wild-type (WT), NOS2 knockout (NOS2-KO), and NOS2-KO + l-NAME treated mice.
- Administered lipopolysaccharide (LPS) to induce endotoxemia.
- Employed stable isotope infusion (l-[phenyl-(2)H(5)]Phe, l-[phenyl-(2)H(2)]Tyr, l-[guanidino-(15)N(2)]Arg, l-[ureido-(13)C; (2)H(2)]citrulline) to study whole-body and intestinal metabolism.
Main Results:
- NOS2 deficiency increased whole-body protein turnover and intestinal glutamine (Gln) uptake and citrulline (Cit) production in nonstimulated conditions.
- LPS administration increased NO and Cit production in WT mice but decreased them in NOS2-KO mice.
- Endotoxemic NOS2-KO + l-NAME mice exhibited high mortality, with surviving mice showing near-zero intestinal protein metabolism.
Conclusions:
- Absence of NOS2 upregulates NOS1 and/or NOS3, enhancing intestinal metabolism under basal and endotoxemic states.
- Reduced intestinal protein metabolism in endotoxemic NOS2-deficient mice may contribute to mortality.
- NOS2 plays a critical role in maintaining intestinal homeostasis during endotoxemia.
