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Participation of endothelium‐derived nitric oxide but not prostacyclin in the gastric mucosal hyperaemia due to acid back‐diffusion
Author(s) -
Lippe Irmgard Th.,
Holzer Peter
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb09043.x
Subject(s) - prostacyclin , nitric oxide , perfusion , chemistry , medicine , endocrinology , hyperaemia , blood flow
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 N G ‐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.