Bilateral adrenalectomy worsens gastric mucosal lesions induced by indomethacin in the rat. Role of enhanced gastric motility.
The mechanism by which bilateral adrenalectomy worsens indomethacin-induced gastric lesions was investigated in rats. In sham-operated rats subcutaneously administered indomethacin produced gastric lesions at doses of 10 mg/kg body wt or greater, in association with lowering of blood glucose levels. In a parallel study, indomethacin induced gastric hypermotility at the same dose levels but had no effect on acid output or mucosal blood flow even at 25 mg/kg body wt. Adrenalectomy (2 wk) itself significantly reduced the blood glucose levels (approximately 50%) and markedly potentiated the ulcerogenic and motility responses caused by indomethacin; the ED50 values dropped to approximately 10 times lower than those in sham-operated rats. Both acid output and mucosal blood flow were significantly reduced by adrenalectomy, but these values were increased after indomethacin treatment (3 mg/kg body wt). The ulcerogenic and motility responses caused by indomethacin were significantly reduced by acute infusion of glucose (25% wt/wt, 1.2 ml/h) intravenously in both sham-operated and adrenalectomized rats, and by subcutaneous administration of hydrocortisone acetate (10 mg/kg body wt for 2 wk) in the latter group. When the motility and the ulcer score were determined in the same animals, a highly significant relationship was found between these two factors in both sham-operated and adrenalectomized rats. These results suggest that (a) the increased gastric motility may be a key element in the pathogenesis of indomethacin-induced lesions and in the mechanism for aggravation of the lesions and in the mechanism for aggravation of the lesions by adrenalectomy, and (b) abrasion of adrenal glands by inducing hypoglycemia may sensitize the system to indomethacin and increase gastric motility.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Nishiwaki
H
H
Okada
M
M
Niida
H
H
Okabe
S
S
D000315:Adrenalectomy; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D007213:Indomethacin / Q000633:toxicity*; D008297:Male; D051381:Rats; D012039:Regional Blood Flow; D013276:Stomach Ulcer / Q000139:chemically induced*
D001786:Blood Glucose; D005947:Glucose; D006854:Hydrocortisone; D007213:Indomethacin