Angiotensin II enhances thrombosis development in renovascular hypertensive rats

Andrzej Mogielnicki; Ewa Chabielska; Robert Pawlak; Janusz Szemraj; Wlodzimierz Buczko

doi:10.1160/TH04-10-0701

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 93(06): 1069-1076
DOI: 10.1160/TH04-10-0701

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Angiotensin II enhances thrombosis development in renovascular hypertensive rats

Andrzej Mogielnicki

¹Department of Pharmacodynamics, Medical University, Bialystok, Poland

,

Ewa Chabielska

²Department of Biopharmacy, Medical University, Bialystok, Poland

,

Robert Pawlak

³Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, USA

,

Janusz Szemraj

⁴Department of Medical Biochemistry, Medical University, Lodz, Poland

,

Wlodzimierz Buczko

¹Department of Pharmacodynamics, Medical University, Bialystok, Poland

› Author Affiliations

Abstract

Summary

There is an increased number of in vitro evidence that angioten-sin II (Ang II) may promote thrombosis. However there are no in vivo experiments exploring the effect of Ang II on thrombus formation. In the present study we have investigated the influence of Ang II on venous thrombosis in renovascular hypertensive rats. Furthermore, we examined the role of AT₁ receptor and Ang II metabolites: angiotensin III (Ang III) and angioten-sin IV (Ang IV) in the mechanisms of Ang II action. The contribution of coagulation and fibrinolytic systems in the mode of Ang II action was also determined. Venous thrombosis was induced by ligation of vena cava. Ang II infused into rats developing venous thrombosis caused dose-dependent increase in thrombus weight, which was partially reversed by losartan, selective AT₁ antagonist. Ang III did not influence the thrombus formation in hypertensive rats, while Ang IV caused a marked increase in thrombus weight only in one of the used doses. Our study shows that Ang II via AT₁ receptor enhances thrombosis development. The prothrombotic effect of Ang II may partially depend on enhanced leukocytes adhesion to endothelial cells accompanied by accelerated fibrin formation and increased plasma level of PAI-1. Moreover, Ang II action is partially mediated by one of its metabolites – Ang IV.

Keywords

Angiotensin - hypertensive rat - haemostasis - venous thrombosis

Full Text

References

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