Long-term dietary L-arginine supplementation increases endothelial nitric oxide synthase and vasoactive intestinal peptide immunoexpression in rat small intestine

Eur J Nutr. 2014 Apr;53(3):813-21. doi: 10.1007/s00394-013-0585-8. Epub 2013 Oct 8.

Abstract

Background and aims: Nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) are important intestinal neurotransmitters that coexist in the gut enteric nervous system and play an important role in intestinal physiology (e.g., absorption, motility, fluid secretion and smooth muscle relaxation). It is also known that cold exposure alters several aspects of gastrointestinal physiology and induces hyperphagia to meet increased metabolic demands, but there are no data regarding NO and VIP involvement in intestinal response during acclimation to cold. The objective of this study was to determine the influence of long-term L-arginine supplementation on the expression of the three isoforms of nitric oxide synthase (NOS) and VIP in small intestine of rats acclimated to room temperature or cold.

Methods: Animals (six per group) acclimated to room temperature (22 ± 1 °C) and cold (4 ± 1 °C), respectively, were treated with 2.25% L-arginine, a substrate for NOSs, or with 0.01% N(ω)-nitro-L-arginine methyl ester, an inhibitor of NOSs, for 45 days. The topographical distribution of VIP and NOSs expression in small intestine was studied by immunohistochemistry, and ImageJ software was used for semiquantitative densitometric analysis of their immunoexpression.

Results: Long-term dietary L-arginine supplementation increases VIP and NOSs immunoexpression at room temperature while at cold increases the endothelial NOS, inducible NOS and VIP but decrease neuronal NOS in rat small intestine.

Conclusion: Our results demonstrate that long-term dietary L-arginine supplementation modulates NOSs and VIP immunoexpression in rat small intestine with respect to ambient temperature, pointing out the eNOS as a predominant NOS isoform with an immunoexpression pattern similar to VIP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / drug effects
  • Animals
  • Arginine / antagonists & inhibitors
  • Arginine / metabolism*
  • Cold Temperature / adverse effects
  • Crosses, Genetic
  • Dietary Supplements*
  • Enterocytes / cytology
  • Enterocytes / drug effects
  • Enterocytes / metabolism
  • Enzyme Inhibitors / pharmacology
  • Immunohistochemistry
  • Interstitial Cells of Cajal / cytology
  • Interstitial Cells of Cajal / drug effects
  • Interstitial Cells of Cajal / metabolism
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism*
  • Intestine, Small / cytology
  • Intestine, Small / drug effects
  • Intestine, Small / metabolism*
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Synthase Type I / antagonists & inhibitors
  • Nitric Oxide Synthase Type I / metabolism
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / chemistry
  • Nitric Oxide Synthase Type II / metabolism
  • Nitric Oxide Synthase Type III / antagonists & inhibitors
  • Nitric Oxide Synthase Type III / chemistry
  • Nitric Oxide Synthase Type III / metabolism*
  • Rats
  • Up-Regulation* / drug effects
  • Vasoactive Intestinal Peptide / agonists*
  • Vasoactive Intestinal Peptide / metabolism

Substances

  • Enzyme Inhibitors
  • Vasoactive Intestinal Peptide
  • Arginine
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos1 protein, rat
  • Nos2 protein, rat
  • Nos3 protein, rat
  • NG-Nitroarginine Methyl Ester