Blood Pressure Reduction and Tissue-Type Plasminogen Activator Release

Abstract

Hypertension is associated with increased risk of thrombotic events including myocardial infarction and stroke. The endothelium plays an important role in limiting intravascular thrombosis, inhibiting coagulation and platelet aggregation, and promoting fibrinolysis. Hrafnkelsdottir et al1 have previously described impaired vascular tissue-type plasminogen activator (t-PA) release in individuals with essential hypertension. In the current issue of Hypertension ,2 this group reports that treatment with either an angiotensin-converting enzyme (ACE) inhibitor or a calcium channel blocker increases stimulated t-PA release from the forearm vasculature. t-PA is synthesized and stored in small, dense granules in the vascular endothelium and released in response to such stimuli as Factor Xa, thrombin, bradykinin, and catecholamines, as well as substance P, the vasopressin analogue desmopressin, methacholine, tumor necrosis factor α, and adenosine and uridine triphosphates (Figure).3 Although some studies suggest that t-PA colocalizes with von Willebrand factor in Weibel-Palade bodies, the preponderance of evidence suggests that t-PA is stored in distinct granules and that the release of t-PA and von Willebrand factor are differentially regulated.4 Although shear stress induces t-PA release from cultured endothelial cells, t-PA release from the intact vasculature appears to …