Published Online
on March 6, 2006

A more recent version of this article appeared on April 1, 2006

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Submitted on December 4, 2005
Revised on January 3, 2006

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

Wilhelm Ridderstråle; Erik Ulfhammer; Sverker Jern; and Thórdís Hrafnkelsdóttir^*

From the Clinical Experimental Research Laboratory, Sahlgrenska University Hospital/Östra, Institute of Medicine, Göteborg University, Göteborg, Sweden.

^* To whom correspondence should be addressed. E-mail: thordis.hrafnkelsdottir{at}hjl.gu.se.

Abstract--The increased risk for myocardial infarction and ischemic stroke in primary hypertension suggests that the condition is associated with prothrombotic mechanisms. We have shown that patients with hypertension have an impaired capacity for acute endothelial tissue-type plasminogen activator (t-PA) release, an important local protective response to prevent formation of intravascular thrombi. The aim of the present study was to investigate whether this impairment could be restored by the lowering of blood pressure. The capacity for acute t-PA release in response to intraarterial infusion of substance P at 8 pmol/min was investigated in a perfused-forearm study in 20 hypertensive patients (12 men and 8 women). Studies were performed when patients were untreated and after 8 weeks of randomized treatment with lisinopril or felodipine that lowered blood pressure by 26/10 and 24/12 mm Hg, respectively. The t-PA release response increased significantly with treatment (ANOVA, P=0.0001), with a similar effect in the 2 treatment groups. The peak release of t-PA increased from 257 (58) to 445 (77) ng/minxL/tissue^-1 (t test, P=0.02). Also, treatment shortened the average time to peak secretion from 6.7 (1.4) to 2.7 (0.3) min (t test, P=0.01). In 6 patients with a delayed secretory peak (9 minutes or later), treatment normalized the response (² test, P=0.008). Antihypertensive therapy restores the capacity for acute t-PA release and improves the rapidity of the response in patients with primary hypertension. Similar responses with the 2 regimens suggest that the improvement is related to the blood pressure reduction as such. This effect may contribute to the thromboprotective effect of antihypertensive treatment.

Key words: endothelium • antihypertensive agents • calcium antagonists • angiotensin antagonists

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