Gastric mucosal damage induced by local intra-arterial administration of Paf in the rat.
1. A technique for the close-arterial administration of substances to the rat stomach in vivo has been developed. 2. Intra-arterial infusion of platelet-activating factor (Paf, 10-50 ng kg-1 min-1 for 10 min) induced macroscopically assessed damage in the corpus mucosa, characterized as vasocongestion and necrosis. 3. The threshold intra-arterial doses of Paf that induced histologically assessed damage in the antrum and corpus of the stomach (10 and 5 ng kg-1 min-1, respectively) produced minimal systemic hypotension (less than 20 mmHg) suggesting a dissociation between these events. 4. Pretreatment with the Paf-antagonist, L-652,731 (2.5 mg kg-1 i.v.) prevented the gastric damage induced by local infusion of Paf. 5. Intravenous infusion of Paf (25 ng kg-1 min-1) did not significantly damage the gastric mucosa, in contrast to the same dose infused locally, yet Paf administered by either route produced a comparable degree of hypotension. Such findings suggest minimal metabolism of Paf during its passage through the gastric circulation. 6. Local intra-arterial infusion of Paf in doses as low as 0.25 ng kg-1 min-1, which had no systemic hypotensive actions, significantly induced gastric damage in the presence of intragastric 20% ethanol. 7. These observations support a local role for Paf in the pathogenesis of gastric irritation and ulceration, such as that observed during endotoxin shock or bacterial infection. The present technique is thus useful for the study of locally administered substances on gastric function and integrity.
Esplugues
J V
JV
Department of Mediator Pharmacology, Wellcome Research Laboratories, Beckenham, Kent.
Whittle
B J
BJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005663:Furans / Q000494:pharmacology; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects*; D007262:Infusions, Intravenous; D007269:Injections, Intra-Arterial; D008297:Male; D010477:Perfusion; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains
D005663:Furans; D010972:Platelet Activating Factor; C047504:2,5-bis(3,4,5-trimethoxyphenyl)tetrahydrofuran