Close-arterial administration of the thromboxane mimetic U-46619 induces damage to the rat gastric mucosa.
The pro-ulcerogenic actions of the thromboxane mimetic, U-46619 on the rat gastric mucosa have been investigated, utilizing a novel technique which allows administration directly into the left gastric artery. Local intra-arterial infusion of U-46619 (100-500 ng/kg/min for 10 min) induced dose-dependent macroscopic damage in both the corpus and antral regions, characterized as vasocongestion, disruption and haemorrhage, with deep penetrating ulcers in the antral mucosa. Vascular congestion, epithelial cell and glandular disruption was observed histologically in both corpus and antral regions. Local intra-arterial infusion of lower doses of U-46619 (25-100 ng/kg/min) significantly disrupted the mucosa in the presence of 10% ethanol in a concentration which itself did not induce macroscopic damage. The damaging actions of U-46619 were substantially reduced by pretreatment with the thromboxane-receptor antagonist, BM 13,177 (5mg/kg i.v.) or 16,16-dimethyl PGE2 (5 micrograms/kg s.c.). These findings support the role of endogenous thromboxane A2 as a local mediator of gastric injury.
Esplugues
J V
JV
Department of Mediator Pharmacology, Wellcome Research Laboratories, Beckenham, Kent, U.K.
Whittle
B J
BJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000818:Animals; D001158:Arteries; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D007261:Infusions, Intra-Arterial; D008297:Male; D011450:Prostaglandin Endoperoxides, Synthetic / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000187:drug effects; D017482:Receptors, Thromboxane; D013270:Stomach / Q000098:blood supply; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology
D011450:Prostaglandin Endoperoxides, Synthetic; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D000431:Ethanol; C040624:sulotroban; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015064:16,16-Dimethylprostaglandin E2