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

Abstract

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.