Regulation of gastric mucosal integrity by endogenous nitric oxide: interactions with prostanoids and sensory neuropeptides in the rat

Br J Pharmacol. 1990 Mar;99(3):607-11. doi: 10.1111/j.1476-5381.1990.tb12977.x.


1. The interactions between nitric oxide (NO), prostacyclin and sensory neuropeptides in the maintenance of gastric mucosal integrity have been investigated in the anaesthetized rat. 2. Administration of either NG-monomethyl-L-arginine (L-NMMA) to inhibit endothelium-derived NO formation, indomethacin to inhibit prostanoid biosynthesis or chronic capsaicin pretreatment to deplete sensory neuropeptides, did not induce acute mucosal injury. 3. In capsaicin-pretreated rats, however, L-NMMA (12.5-100 mg kg-1 i.v.) dose-dependently induced acute mucosal damage, characterized as vasocongestion and haemorrhagic necrosis. The enatiomer D-NMMA (100 mg kg-1 i.v.) did not induce any detectable mucosal damage. 4. This mucosal injury induced by L-NMMA was inhibited by concurrent administration of L-arginine (300 mg kg-1 i.v.). 5. In indomethacin (5 mg kg-1 i.v.)-pretreated rats, L-NMMA also induced mucosal damage. Furthermore, following indomethacin administration in capsaicin-pretreated rats, L-NMMA induced widespread, severe haemorrhagic necrotic damage. 6. These findings suggest a role for endogenous NO formed from L-arginine, acting in concert with prostacyclin and sensory neuropeptides, in the modulation of gastric mucosal integrity.

MeSH terms

  • Animals
  • Arginine / analogs & derivatives
  • Arginine / antagonists & inhibitors
  • Arginine / pharmacology
  • Blood Pressure / drug effects
  • Capsaicin / pharmacology
  • Epoprostenol / pharmacology
  • Gastric Mucosa / physiology*
  • Indomethacin / pharmacology
  • Male
  • Neurons, Afferent / physiology*
  • Neuropeptides / pharmacology*
  • Nitric Oxide / pharmacology*
  • Prostaglandins / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Stomach Ulcer / chemically induced
  • omega-N-Methylarginine


  • Neuropeptides
  • Prostaglandins
  • omega-N-Methylarginine
  • Nitric Oxide
  • Arginine
  • Epoprostenol
  • Capsaicin
  • Indomethacin