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Title: The Peripheral Serotonergic System and Platelet Aggregation in Cyclosporin A-Induced Hypertensive Rats
Authors: Reis, Flávio 
Tavares, Paula 
Ribeiro, C. A. Fontes 
Antunes, Ferrer 
Teixeira, Frederico 
Keywords: Cyclosporin A; Hypertension; Thromboembolic complications; Serotonin; Aggregation
Issue Date: 1999
Citation: Thrombosis Research. 96:5 (1999) 365-372
Abstract: Cyclosporin A plays an important role in preventing rejection in allograft transplant recipients. However, the therapeutic use of cyclosporin A is associated with increased incidence of thromboembolic complications and drug-related hypertension. In order to study the mechanisms by which cyclosporin A induces these abnormal pathophysiological situations, we have assessed the platelet serotonin contents and whole blood platelet aggregation in control rats as well as in rats treated (orally) with 30 and 5 mg/kg/day of cyclosporin A, after 2 and 7 weeks of treatment. These doses correspond respectively to CsA "peak" and "trough" concentrations achieved in human blood in clinical practice (immediately following an intake of a daily dose of CsA and when the blood concentration stabilizes, respectively). Both trough and peak doses caused an increase in blood pressure after 2 and 7 weeks. Platelet serotonin content decreased in the cyclosporin-treated groups, in contrast with the control. Collagen-induced whole blood platelet aggregation increased drastically for the peak concentration-treated group, while adenosine 5'-diphosphate-induced platelet aggregation did not reach statistical significance. Finally, in vitro platelet thromboxane A2 generation increased in cyclosporin A concentrations when platelets were stimulated with either collagen or adenosine 5'-diphosphate. In conclusion, both tested cyclosporin A concentrations induced important changes in platelet serotonin and thromboxane content and aggregation, factors which may play a decisive role in the development and/or maintenance of hypertension and thrombotic complications.
DOI: 10.1016/S0049-3848(99)00115-2
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais

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