Participation of endothelium-derived nitric oxide but not prostacyclin in the gastric mucosal hyperaemia due to acid back-diffusion

Br J Pharmacol. 1992 Mar;105(3):708-14. doi: 10.1111/j.1476-5381.1992.tb09043.x.


1. The possible participation of prostacyclin and nitric oxide (NO) in the gastric mucosal hyperaemic response to acid back-diffusion through a disrupted gastric mucosal barrier was examined. The experiments were carried out on anaesthetized rats in which acid back-diffusion was elicited by gastric perfusion with dilute ethanol in 0.15 M HCl and gastric mucosal blood flow (MBF) was measured by the hydrogen gas clearance technique. 2. Indomethacin (28 mumols kg-1, s.c.), an inhibitor of the formation of cyclo-oxygenase products including prostacyclin, failed to alter mean arterial blood pressure (MAP), basal MBF and the hyperaemic response to acid back-diffusion in urethane-anaesthetized rats. 3. NG-nitro-L-arginine methyl ester (L-NAME; 13 and 43 mumols kg-1, i.v.), an inhibitor of endothelium-derived NO formation, increased MAP in a dose-dependent manner. Whilst basal MBF in urethane-anaesthetized rats was not changed, the increase in MBF caused by gastric perfusion with dilute ethanol in acid was dose-dependently depressed by L-NAME. The loss of H+ ions from the gastric lumen, an indirect measure of acid back-diffusion, was significantly enhanced by 43 mumols kg-1 L-NAME. In contrast, D-NAME (13 and 43 mumols kg-1) was without effect on MAP, basal and stimulated MBF, and acid back-diffusion. 4. Unlike in urethane-anaesthetized rats, L-NAME led to a significant reduction of basal MBF in phenobarbitone-anaesthetized rats. MAP in the phenobarbitone-anaesthetized rats was significantly higher than in urethane-anaesthetized rats, and the hypertensive effect of L-NAME under phenobarbitone anaesthesia was significantly smaller than under urethane anaesthesia.5. The rise in MBF brought about by acid back-diffusion was blocked by L-NAME administered to phenobarbitone-anaesthetized rats. Infusion of L-arginine (120 pmol kg -1 min- ', i.v.) led to a partial, but significant, reversal of the effects of L-NAME on MAP and the hyperaemia due to acid back-diffusion.6. These findings indicate that endothelium-derived NO plays an important mediator role in the gastric mucosal vasodilatation caused by back-diffusion whilst vasodilator prostanoids such as prostacyclin are not involved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthesia
  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Blood Pressure / drug effects
  • Diffusion
  • Endothelium, Vascular / physiology*
  • Epoprostenol / physiology*
  • Female
  • Gastric Acid / physiology*
  • Gastric Mucosa / blood supply
  • Gastric Mucosa / physiology*
  • Heart Rate / drug effects
  • Hyperemia / physiopathology*
  • Indomethacin / pharmacology
  • Male
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Regional Blood Flow / physiology
  • Urethane


  • Nitric Oxide
  • Urethane
  • Arginine
  • Epoprostenol
  • NG-Nitroarginine Methyl Ester
  • Indomethacin