Enteral arginine does not increase superior mesenteric arterial blood flow but induces mucosal growth in neonatal pigs

Arginine is a nutritionally essential amino acid in neonates and is required for protein synthesis and growth. Although arginine production in adults occurs mainly in the kidneys, in the neonate arginine is exclusively synthesized in gut epithelial cells from amino acid precursors. Except for serving as a building block for proteins, arginine has been shown to exert beneficial effects on intestinal integrity and function, because it is the major amino acid precursor of polyamines essential for gut healing, an enhancer of cell migration, an activator of protein synthesis, and the sole physiological precursor for NO that regulates vasodilatation and blood flow. Arginine supplementation has been shown to improve intestinal integrity in ischemia-reperfusion models and low plasma levels are associated with necrotizing enterocolitis. We hypothesized that enteral arginine is a specific stimulus for neonatal intestinal blood flow and mucosal growth under conditions of total parenteral nutrition (TPN) or partial enteral nutrition (PEN). We first tested the dose dependence and specificity of acute (3 h) enteral arginine infusion on superior mesenteric artery (SMA) blood flow in pigs fed TPN or PEN. We then determined whether chronic (4 d) arginine supplementation of PEN increases mucosal growth and if this was affected by treatment with the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME).

Acute enteral arginine infusion increased plasma arginine dose dependently in both TPN and PEN groups, but the plasma response was markedly higher (100–250%) in the PEN group than in the TPN group at the 2 highest arginine doses. Baseline SMA blood flow was 90% higher in the PEN (2.37 ± 0.32 L•kg^-1•h^-1) pigs than in the TPN pigs (1.23 ± 0.17 L•kg^-1•h^-1), but was not affected by acute infusion individually of arginine, citrulline, or other major gut fuels. Chronic dietary arginine supplementation in PEN pigs induced mucosal growth in the intestine, but this effect was not prevented by treatment with L-NAME. Intestinal crypt cell proliferation, protein synthesis, and phosphorylation of mTOR (mammalian target of rapamycin) and p70S6 kinase were not affected by dietary arginine.

We conclude that PEF, but not acute enteral arginine, increases SMA blood flow in the neonatal pig. Furthermore, supplementing arginine in PEF modestly increases intestinal mucosal growth and was NO independent.