Increased microvascular permeability and lesion formation during gastric hypermotility caused by indomethacin and 2-deoxy-D-glucose in the rat.
The relationship between lesion formation, gastric motility, and vascular permeability was examined in rats using indomethacin and 2-deoxy-D-glucose (2DG). Both indomethacin (25 mg/kg s.c.) and 2DG (100 mg/kg/h i.v.) produced gastric hypermotility and induced lesions, mostly confined to the rugal crests of the mucosal folds; the onset of hypermotility preceded appearance of the lesions in both cases. The mucosal microvascular permeability as determined by the amount of extravasated dye (Evans blue) was increased in response to these two agents, and the permeability responses also preceded appearance of the lesions. Both the increased vascular permeability and the severity of lesions were significantly reduced when the hypermotility was inhibited by pretreatment with atropine (3 mg/kg s.c.). The severity of the lesions were also markedly reduced or worsened, respectively, by hydrocortisone (10 mg/kg s.c.) or N-ethylmaleimide (10 mg/kg s.c.) at the doses that significantly decreased or enhanced the vascular permeability responses caused by indomethacin and 2DG. These results suggest that the enhanced gastric motility as induced by indomethacin and 2DG may cause microcirculatory disturbances in the specific sites of the mucosa (mucosal folds), probably by abnormal compression of the gastric wall, leading to the increased microvascular permeability and cellular damage.
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
K
K
Takeuchi
M
M
Okada
S
S
Ebara
H
H
Osano
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D003847:Deoxyglucose / Q000494:pharmacology*; D005070:Evans Blue / Q000493:pharmacokinetics; D005753:Gastric Mucosa / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D005070:Evans Blue; D003847:Deoxyglucose; D007213:Indomethacin