Antithrombotic Effect of Captopril and Losartan Is Mediated by Angiotensin-(1-7)
作者:
Iwona Kucharewicz,
Robert Pawlak,
Tomasz Matys,
Dariusz Pawlak,
Wlodzimierz Buczko,
期刊:
Hypertension: Journal of The American Heart Association
(OVID Available online 2002)
卷期:
Volume 40,
issue 5
页码: 774-779
ISSN:0194-911X
年代: 2002
出版商: OVID
关键词: angiotensin;venous thrombosis;captopril;losartan;nitric oxide;prostacyclin;rats
数据来源: OVID
摘要:
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 (NG-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.
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