INVESTIGATION OF THE VASODILATOR AND ANTISECRETORY ROLE OF PROSTAGLANDINS IN THE RAT GASTRIC MUCOSA BY USE OF NON‐STEROIDAL ANTI‐INFLAMMATORY DRUGS

Abstract

The effects of non‐steroidal anti‐inflammatory drugs on gastric acid secretion and mucosal blood flow were studied in the rat. Indomethacin, in ulcerogenic doses, caused a dose‐dependent rise in pentagastrin‐stimulated acid secretion, but decreased mucosal blood flow per unit acid secretion. During resting conditions, indomethacin had no significant effect on acid output, but reduced mucosal blood flow. Pretreatment with indomethacin, phenylbutazone or meclofenamate potentiated the secretory response to dibutyryl cyclic adenosine 3′,5′‐monophosphate. Indomethacin markedly reduced the mucosal prostaglandin‐like activity at a time when mucosal erosion formation had reached steady levels. These results provide evidence that prostaglandins have a local role in the regulation of blood flow and acid secretion in the rat gastric mucosa, and suggest that non‐steroidal anti‐inflammatory drugs cause mucosal erosions by disrupting these processes. 1975 British Pharmacological Society