Prostacyclin is required for t-PA release after venous occlusion.
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.
Iacoviello
L
L
Laboratory of Thrombosis Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Santa Maria Imbaro, Italy.
De Curtis
A
A
D'Adamo
M C
MC
Amore
C
C
Buczko
W
W
De Gaetano
G
G
Donati
M B
MB
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005342:Fibrinolysis / Q000187:drug effects / Q000502:physiology*; D016285:Iloprost / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D014682:Vena Cava, Inferior / Q000502:physiology*
D007093:Imidazoles; C029166:dazoxiben; D015121:6-Ketoprostaglandin F1 alpha; D010959:Tissue Plasminogen Activator; D013930:Thromboxane-A Synthase; D016285:Iloprost; D001241:Aspirin