Attenuating effect of antithrombin III on the fibrinolytic activation and microvascular derangement in rat gastric mucosa.
The roles for the fibrinolytic activation and disorder of coagulation in formation of gastric ulcer induced by microvascular derangement were investigated. The rat stomach was exposed and repeated electrical stimuli (RES) were applied on the small arterial wall close to the lesser curvature to induce mucosal microcirculatory disturbances. The level of tissue-type plasminogen activator (t-PA), a key enzyme for fibrinolytic activity, in the regional blood of the stomach was significantly elevated immediately after RES. At 5 min after RES, the leakage of FITC-labeled albumin and thrombus formation in the mucosal microvasculature were visually demonstrated by using an intravital microscopic system. At 30 min, hemorrhagic erosions and linear ulcers were observed in the gastric mucosa. Pretreatment with human antithrombin-III (AT-III) in the range of 0.1-10 U/kg dose-dependently attenuated both the fibrinolytic activation and microvascular alteration promoted by RES. Human AT-III also prevented RES-induced gastric mucosal injury. Thrombin inhibitory activity in the gastric vein decreased (69.0 +/- 2.1%) just after RES, and further reduced at 30 min (47.7 +/- 5.3%). The present study suggests a hypothesis that human AT-III has a preventive effect on the gastric mucosal hemorrhagic changes via attenuating the fibrinolytic activation and subsequent microcirculatory disturbances.
Kurose
I
I
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Miura
S
S
Fukumura
D
D
Suzuki
M
M
Nagata
H
H
Sekizuka
E
E
Morishita
T
T
Tsuchiya
M
M
D000818:Animals; D000990:Antithrombin III / Q000494:pharmacology* / Q000627:therapeutic use; D002199:Capillary Permeability; D004597:Electroshock / Q000009:adverse effects; D005342:Fibrinolysis / Q000187:drug effects*; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects*; D006471:Gastrointestinal Hemorrhage / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D010959:Tissue Plasminogen Activator / Q000032:analysis
D000990:Antithrombin III; D010959:Tissue Plasminogen Activator