Pharmacological modulation of fibrinolytic response - in vivo and in vitro studies

Fibrinolysis is an action of converting plasminogen by its activators,like tissue- or urokinase-type plasminogen activators (t-pa,u-pa),to plasmin,which in turn cleaves fibrin,thereby causing clot dissolution and restoration of blood flow. endothelial cells release t-pa,prostacyclin (pgi2) and nitric oxide (no),the potent factors playing a crucial role in regulation of the fibrinolytic system. since blood platelets can release not only prothrombotic,but also antifibrinolytic factors,like plasminogen activator inhibitor type-1 (pai-1),they are involved in fibrynolysis regulation. therefore agents enhancing fibrinolysis can be preferred pharmacologicals in many cardiovascular diseases. this review describes mechanisms by which major cardiovascular drugs (renin-angiotensin-aldosterone system inhibitors,statins,adrenergic receptors and calcium channel blockers,aspirin and 1-methylnicotinamide) influence fibrinolysis. the presented data indicate,that the influence of these drugs on endothelium-blood platelets interactions via no/pgi2 pathway is fundamental for its antithrombotic and profibrinolytic action. we also described new approaches for intravital confocal real-time imaging as a tool useful to investigate mechanisms of thrombus formation and the effects of drugs affecting haemostasis and mechanisms of their action in the circulation. © 2015 institute of pharmacology,polish academy of sciences.