AJP - Heart and Circulatory Physiology, Vol 266, Issue 2 429-H434, Copyright © 1994 by American Physiological Society
Prostacyclin is required for t-PA release after venous occlusion
L. Iacoviello, A. De Curtis, M. C. D'Adamo, C. Amore, W. Buczko, G. De Gaetano and M. B. Donati
Laboratory of Thrombosis Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Santa Maria Imbaro, Italy.
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 (mean +/- SE,
P < 0.002). This increase was prevented by aspirin at high (100 mg/kg
i.v.) but not at low doses (1 mg/kg i.v.). Dazoxiben (10 mg/kg i.v.), an
inhibitor of thromboxane synthase, was ineffective on the fibrinolytic
response. Both the basal levels of 6-ketoprostaglandin F1 alpha 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.
