Potentiation of aspirin-induced gastric lesions by exposure to cold in rats. Role of acid secretion, mucosal blood flow, and gastric mucosal prostanoid content.
We investigated the mechanism by which exposure to cold sensitizes rats to the formation of gastric lesions after a low dose of aspirin (50 mg/kg). Six times more lesions were produced by aspirin plus cold than by aspirin alone. Three hypotheses were studied to explain the synergism of aspirin plus cold on lesion formation: gastric acid hypersecretion, reduced gastric mucosal blood flow, and decreased prostanoid synthesis by the stomach. Cold, and cold plus aspirin, stimulated gastric acid secretion (to a similar extent), whereas aspirin had no effect. Gastric mucosal blood flow, measured by the hydrogen gas clearance method, was decreased by cold, aspirin, and aspirin plus cold, and the extent of decrease was similar. Prostanoid generation [prostaglandin E2 (PGE2), PGF2 alpha, 6-keto PGF1 alpha, and thromboxane B2] by the gastric corpus mucosa was not affected by cold, but was reduced equally (by at least 90%) in animals receiving aspirin alone or aspirin plus cold. After oral administration of aspirin, the plasma contained mostly salicylic acid (98%), whereas the gastric mucosa contained mostly aspirin (80%-85%). We conclude that the synergism of aspirin plus cold on the formation of gastric lesions probably results from the combined effects of three factors: increased secretion of acid (because of exposure to cold) that is in contact with a gastric mucosa in which blood flow is reduced (because of exposure to cold or to aspirin), and in which the synthesis of cytoprotective prostaglandins is inhibited (by aspirin). Such mucosa may be particularly vulnerable to the damaging effect of hyperacidity.
Robert
A
A
Safety Pharmacology, Upjohn Company, Kalamazoo, Michigan.
Leung
F W
FW
Kaiser
D G
DG
Guth
P H
PH
D000818:Animals; D001241:Aspirin / Q000633:toxicity*; D003080:Cold Temperature / Q000009:adverse effects*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow; D013276:Stomach Ulcer / Q000209:etiology*
D011453:Prostaglandins; D001241:Aspirin