Protective effects of arginine-vasopressin on aspirin-induced gastric mucosal damage in anaesthetized dogs

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.