The role of vascular cyclooxygenase pathway on tissue-type plasminogen activator (t-PA) release after venous occlusion was studied in anesthetized rats. After the inferior vena cava was clamped for 30 min, fibrinolytic activity increased from 143.7 ± 14.5 to 209.5 ± 10.3 mm2 (means ± SE, P <0.002). This increase was prevented by aspirin at high (100 mg/kg iv) but not at low doses (1 mg/kg iv). Dazoxiben (10 mg/kg iv), an inhibitor of thromboxane synthase, was ineffective on the fibrinolytic response. Both the basal levels of 6-ketoprostaglandin F(1α) and its increase after venous occlusion were suppressed by 100 mg/kg aspirin administration (from 0.64 ± 0.2 to 0.05 ± 0.002 ng/ml before occlusion, P <0.001; and from 1.08 ± 0.2 to 0.06 ± 0.002 ng/kg after occlusion, P <0.001), whereas they were both unaffected by aspirin at low doses (from 0.53 ± 0.06 before to 1.20 ± 0.08 ng/ml after stasis). Moreover, iloprost, a stable analogue of prostacyclin, reversed the aspirin inhibitory effects on fibrinolytic activity by restoring t-PA vascular release after venous stasis. Our results provide experimental evidence that an intact cyclooxygenase pathway in vascular wall is required for the fibrinolytic activity increase after venous occlusion in rats.
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|Issue number||2 35-2|
|Publication status||Published - 1994|
- vascular endothelium
ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)