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

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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 μmol 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 μmol 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 μmol kg−1 l-NAME. In contrast, d-NAME (13 and 43 μmol 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 μmol kg−1 min−1, 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.