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(Hypertension. 2006;47:648.)
© 2006 American Heart Association, Inc.

Editorial Commentaries

Blood Pressure Reduction and Tissue-Type Plasminogen Activator Release

Nancy J. Brown

From the Vanderbilt University Medical Center, Nashville, Tenn.

Correspondence to Nancy J. Brown, Vanderbilt University Medical Center, 560 Robinson Research Building, Nashville, TN 37232-6602. E-mail nancy.j.brown@vanderbilt.edu

An extract of the first 250 words of the full text is provided, because this article has no 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 , 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 be flow independent. NO does not stimulate t-PA release and may even impede the exocytosis of t-PA.^5,6 t-PA is rapidly released in response to increases in intracellular calcium, but the molecular mechanisms underlying the exocytosis of t-PA have not been elucidated in detail.⁴

View larger version (32K): [in this window] [in a new window]   t-PA is synthesized in endothelial cells and both constitutively released and stored in small dense granules. Agonists, acting at . . . [Full Text of this Article]

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Impaired Capacity for Stimulated Fibrinolysis in Primary Hypertension Is Restored by Antihypertensive Therapy

Wilhelm Ridderstråle, Erik Ulfhammer, Sverker Jern, and Thórdís Hrafnkelsdóttir
Hypertension 2006 47: 686-691. [Abstract] [Full Text] [PDF]

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