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-(beta-mercapto-beta,beta-cyclopenta-methylene-propionic acid), 2-(o-methyl)tyrosine-Arg8-vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)
Hung
C R
CR
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Wang
J J
JJ
Chang
W C
WC
Shen
C L
CL
D000818:Animals; D001127:Arginine Vasopressin / Q000627:therapeutic use*; D001241:Aspirin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D004285:Dogs; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D006339:Heart Rate / Q000187:drug effects; D006859:Hydrogen / Q000378:metabolism; D008297:Male; D011863:Radioimmunoassay; D012964:Sodium / Q000378:metabolism; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control; D014628:Vagotomy
D001127:Arginine Vasopressin; D006859:Hydrogen; D012964:Sodium; D015232:Dinoprostone; D001241:Aspirin