title: Enteral arginine does not increase superior mesenteric arterial blood flow but induces mucosal growth in neonatal pigs.
abstract: Arginine is an essential amino acid in neonates synthesized by gut epithelial cells and a 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, N(G)-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 mammalian target of rapamycin and p70S6 kinase were not affected by dietary arginine. We conclude that partial enteral feeding, but not acute enteral arginine, increases SMA blood flow in the neonatal pig. Furthermore, supplementing arginine in partial enteral feeding modestly increases intestinal mucosal growth and was NO independent.
authors.affiliation: Department of Pediatrics, Neonatology, Erasmus MC-Sophia Children's Hospital, Rotterdam 3015 GJ, The Netherlands.
authors.forename: Patrycja J
authors.initials: PJ
authors.lastname: Puiman
authors.forename: Barbara
authors.initials: B
authors.lastname: Stoll
authors.forename: Johannes B
authors.initials: JB
authors.lastname: van Goudoever
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Burrin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000008:administration & dosage* / Q000097:blood; D019587:Dietary Supplements; D004750:Enteral Nutrition; D007413:Intestinal Mucosa / Q000254:growth & development*; D017538:Mesenteric Artery, Superior / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000502:physiology; D009929:Organ Size; D010289:Parenteral Nutrition, Total; D013152:Splanchnic Circulation; D013552:Swine
chemical_list: D009569:Nitric Oxide; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester