The protective effects of graded doses of arginine-vasopressin (AVP) on acidified acetylsalicylic acid (ASA) solution-induced changes in gastric prostaglandin E2 (PGE2) secretion, mucus production, acid back-diffusion and mucosal damage were studied in the bilateral truncal vagotomized stomach of anaesthetized dogs. After 1-4 h intragastric irrigation of the stomach with AVP (1-100 ng kg-1) plus 20 mM acidified ASA solution, a significant (P <0.05) inhibition in gastric mucosal lesions and acid back-diffusion produced by acidified ASA solution was observed. The reduction in the gastric PGE2 secretion and in mucus production provoked by the same dose of acidified ASA solution was also diminished. Furthermore, a correlation (r = 0.883; P <0.01) between AVP-induced inhibition in ASA-provoked reduction in gastric PGE2 secretion and in mucus production was found. During the experiment, the heart rate, the peripheral arterial blood pressure and the gastric arterial blood pressure were not altered by AVP (1-100 ng kg-1). Thus, intragastric AVP protects gastric mucosa against ASA-induced damage without producing cardiovascular side effects. The inhibitory effects of AVP (100 ng kg-1) on acidified ASA-induced reduction in PGE2 and mucus secretion, as well as on ASA-induced enhancement in acid back-diffusion and erosion production were dose-dependently reversed by a specific V1 antagonist, 1-(β-mercapto-β,β-cyclopentamethylene-propionic acid), 2-(o-methyl)tyrosine-Arg8-vasopressin. From the above results, it is suggested that the protective effects of intragastric AVP on gastric mucosa against acidified ASA-induced damage is at least partly due to stimulation of the biosynthesis of gastric PGE2, which may contribute to the increase in the gastric mucus secretion and to the decrease in acid back-diffusion. Furthermore, the endogenous PGE2 stimulated by AVP may be mediated by V1-receptor activation.
|Number of pages||6|
|Journal||Journal of Pharmacy and Pharmacology|
|Publication status||Published - 1994|
ASJC Scopus subject areas
- Pharmaceutical Science