Aspirin-induced gastric ulcers in cats. Prevention by prostacyclin.
Gastric ulcers were produced in conscious cats in 3 hr by simultaneous intravenous or intragastric administration of acetylsalicylic acid (ASA), plus intravenous infusion of histamine (80 micrograms/kg/hr), pentagastrin (8 micrograms/kg/hr), or intragastric instillation of HCl. The formation of these ulcers was accompanied by almost complete inhibition of prostaglandin (PG) biosynthesis, suggesting that the withdrawal of normal protection of gastric mucosa by PGs may be major factor in pathogenesis of ASA-induced gastric lesions. Prostacyclin (PGI2), infused at a dose producing about 50% inhibition of histamine or pentagastrin-induced acid secretion, significantly reduced the formation of gastric ulcers produced by ASA + histamine or pentagastrin. Inhibition of gastric acid secretion by about 50% using ranitidine, a new H2-receptor antagonist, also decreased the formation of gastric ulcers induced by ASA + gastric secretagogue, but the degree of this reduction was significantly smaller than after PGI2. In addition, PGI2 decreased significantly the severity of gastric ulcers produced by a combination of ASA plus gastric perfusion of HCl, the antiulcer effect being more pronounced when PGI2 infusion was started prior to, rather than during, ASA administration. This study confirms that the administration of ASA plus gastric secretagogue or gastric instillation of HCl is a reliable model of gastric ulcerations probably resulting from withdrawal of biosynthesis of mucosal PGs and shows that PGI2 is capable of preventing the formation of these ulcers by means other than its effect on gastric acid secretion.
D000818:Animals; D000897:Anti-Ulcer Agents; D001241:Aspirin / Q000009:adverse effects; D002415:Cats; D011464:Epoprostenol / Q000627:therapeutic use*; D005663:Furans / Q000009:adverse effects; D005744:Gastric Acid / Q000378:metabolism; D006632:Histamine / Q000009:adverse effects; D006635:Histamine H2 Antagonists / Q000009:adverse effects; D006728:Hormones / Q000009:adverse effects; D006851:Hydrochloric Acid / Q000009:adverse effects; D010418:Pentagastrin / Q000009:adverse effects; D011448:Prostaglandin Antagonists; D011453:Prostaglandins / Q000627:therapeutic use*; D011899:Ranitidine; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*
D000897:Anti-Ulcer Agents; D005663:Furans; D006635:Histamine H2 Antagonists; D006728:Hormones; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D006632:Histamine; D011899:Ranitidine; D011464:Epoprostenol; D010418:Pentagastrin; D006851:Hydrochloric Acid; D001241:Aspirin