Role of nitric oxide-related inhibition in intestinal function: relation to vasoactive intestinal polypeptide

Am J Physiol. 1994 Jan;266(1 Pt 1):G31-9. doi: 10.1152/ajpgi.1994.266.1.G31.


This study examined the role of nitric oxide (NO) in tonic inhibition of motor activity in isolated, perfused canine ileal segments. Brief addition of N omega-nitro-L-arginine methyl ester (L-NAME) to the perfusate caused, after a delay, a concentration-dependent persistent increase in tonic and phasic activity of circular muscle. This increased motor activity was prevented or reversed by addition of L- but not D-arginine to the perfusate. Removal of Ca2+ or addition of 10(-7) M omega-conotoxin (GVIA) to the perfusate markedly reduced this response. The motor activity induced by L-NAME was accompanied by loss of distal inhibition and enhanced excitation to low-frequency field stimulation. L-NAME infusion significantly reduced tonic vasoactive intestinal polypeptide (VIP) output, sodium nitroprusside increased VIP output, but L-arginine infusion did not restore VIP output. Atropine (10(-7) M) and/or hexamethonium (10(-4) M) reduced the motor response to L-NAME by 75%. Atropine reduced and hexamethonium nearly abolished VIP output. We conclude that there is tonic Ca(2+)-dependent NO output from perfused intestinal segments dependent on nerves with N-Ca channels, that NO acts to inhibit muscle directly and by inhibiting release of excitatory mediators, and that this output is the primary inhibitory determinant of contractile activity.

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Calcium / physiology
  • Calcium Channel Blockers / pharmacology
  • Dogs
  • Electric Stimulation
  • Extracellular Space / metabolism
  • Gastrointestinal Motility / drug effects
  • Gastrointestinal Motility / physiology
  • Intestines / physiology*
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide / physiology*
  • Osmolar Concentration
  • Peptides / pharmacology
  • Receptors, Nicotinic / physiology
  • Vasoactive Intestinal Peptide / metabolism
  • Vasoactive Intestinal Peptide / physiology*
  • omega-Conotoxin GVIA


  • Calcium Channel Blockers
  • Peptides
  • Receptors, Nicotinic
  • Nitric Oxide
  • Vasoactive Intestinal Peptide
  • omega-Conotoxin GVIA
  • Arginine
  • Acetylcholine
  • Calcium
  • NG-Nitroarginine Methyl Ester