Inhibition of platelet activation in congestive heart failure by aldosterone receptor antagonism and ACE inhibition

Andreas Schäfer; Daniela Fraccarollo; Steven Hildemann; Michael Christ; Martin Eigenthaler; Anna Kobsar; Ulrich Walter; Johann Bauersachs

doi:10.1055/s-0037-1613404

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2003; 89(06): 1024-1030
DOI: 10.1055/s-0037-1613404

Platelets and Blood Cells

Schattauer GmbH

Inhibition of platelet activation in congestive heart failure by aldosterone receptor antagonism and ACE inhibition

Authors

Andreas Schäfer

¹Medizinische Universitätsklinik Würzburg, Germany
Daniela Fraccarollo

¹Medizinische Universitätsklinik Würzburg, Germany
Steven Hildemann

²Pharmacia Corporation, New Jersey, USA
Michael Christ

³Klinik für Innere Medizin, Kardiologie, Philipps-Universität Marburg, Germany
Martin Eigenthaler

⁴Institut für Klinische Biochemie und Pathobiochemie, Universitätsklinik Würzburg, Germany
Anna Kobsar

⁴Institut für Klinische Biochemie und Pathobiochemie, Universitätsklinik Würzburg, Germany
Ulrich Walter

⁴Institut für Klinische Biochemie und Pathobiochemie, Universitätsklinik Würzburg, Germany
Johann Bauersachs

¹Medizinische Universitätsklinik Würzburg, Germany

Abstract

Summary

An increased risk of thrombembolic events in congestive heart failure (CHF) has been attributed to a hypercoagulable state including vascular endothelial dysfunction and platelet activation.

After experimental myocardial infarction, male Wistar rats were treated with placebo, the ACE inhibitor trandolapril, the selective aldosterone receptor antagonist eplerenone or the combination of both, for 10 weeks. Platelet-bound fibrinogen and surface-expressed P-selectin were not modulated in rats without CHF compared with sham-operated animals, but were significantly increased in CHF rats (LVEDP>15mmHg). In CHF rats, ACE inhibition significantly reduced platelet P-selectin expression while bound fibrinogen was not modulated. Eplerenone reduced P-selectin expression to a comparable extent, while platelet-bound fibrinogen was normalised. Combination therapy with eplerenone and trandolapril completely abolished both the increased P-selectin expression as well as fibrinogen binding. Phosphorylation of platelet vasodila-tor-stimulated phosphoprotein (VASP) at both Ser¹⁵⁷ and Ser²³⁹, which reflects the activity of platelet inhibitors including nitric oxide, was significantly reduced in platelets from placebo-treated CHF rats, and was completely normalised by combination treatment, but only marginally increased by either mono-therapy.

The results show that platelet activation was evident only in CHF rats. Monotherapy with ACE inhibition or eplerenone partially reduced this increased platelet activation, which was completely rescued to basal levels by combination therapy. Increased nitric oxide bioavailability can only partially explain the reduced platelet activation by eplerenone and ACE inhibition.

Keywords

Heart failure - platelets - infarction - aldosterone - nitric oxide

Full Text

References

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