Published Online
on September 23, 2002

A more recent version of this article appeared on November 1, 2002

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Submitted on February 21, 2002
Revised on April 8, 2002

Antithrombotic Effect of Captopril and Losartan Is Mediated by Angiotensin-(1-7)

Iwona Kucharewicz; Robert Pawlak; Tomasz Matys; Dariusz Pawlak; and Wlodzimierz Buczko^*

From the Department of Pharmacodynamics, Medical Academy of Bialystok, Bialystok, Poland.

^* To whom correspondence should be addressed. E-mail: pharmdyn{at}amb.edu.pl.

Abstract—It is well established that renin-angiotensin system blockers exert NO/prostacyclin-dependent antithrombotic effects. Because some beneficial effects of these drugs are mediated by angiotensin (Ang)-(1-7), in the present study we examined if their antithrombotic action could be mediated by Ang-(1-7). Intravenous infusion of Ang-(1-7) (1, 10, or 100 pmol/kg per minute for 2 hours) into rats developing venous thrombosis caused 50% to 70% reduction of the thrombus weight. This effect was dose-dependently reversed by cotreatment with A-779 (selective Ang-[1-7] receptor antagonist) or EXP 3174 (angiotensin type 1 receptor antagonist) but not by PD 123,319 (angiotensin type 2 receptor antagonist). Similarly, the antithrombotic effects of captopril (ACE inhibitor) and losartan (angiotensin type 1 receptor blocker) were attenuated by A-779 in a dose-dependent manner. The effect of Ang-(1-7) was completely abolished by concomitant administration of NO synthase inhibitor (N^G-nitro-L-arginine methyl ester) and prostacyclin synthesis inhibitor (indomethacin), as has been shown previously for captopril and losartan. Thus, the antithrombotic effect of renin-angiotensin system blockers involves Ang-(1-7)-evoked release of NO and prostacyclin.

Key words: angiotensin • venous thrombosis • captopril • losartan • nitric oxide • prostacyclin • rats

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