The Peripheral Serotonergic System and Platelet Aggregation in Cyclosporin A-Induced Hypertensive Rats
Autor(a) principal: | |
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Data de Publicação: | 1999 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/4844 https://doi.org/10.1016/S0049-3848(99)00115-2 |
Resumo: | 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. |
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The Peripheral Serotonergic System and Platelet Aggregation in Cyclosporin A-Induced Hypertensive RatsCyclosporin AHypertensionThromboembolic complicationsSerotoninAggregationCyclosporin 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.http://www.sciencedirect.com/science/article/B6T1C-3Y4C5D7-4/1/157b7272bc9cfd3ff94f5888dc32dc261999info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleaplication/PDFhttp://hdl.handle.net/10316/4844http://hdl.handle.net/10316/4844https://doi.org/10.1016/S0049-3848(99)00115-2engThrombosis Research. 96:5 (1999) 365-372Reis, FlávioTavares, PaulaRibeiro, C. A. FontesAntunes, FerrerTeixeira, Fredericoinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2021-10-18T10:14:52Zoai:estudogeral.uc.pt:10316/4844Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:43:29.026790Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
The Peripheral Serotonergic System and Platelet Aggregation in Cyclosporin A-Induced Hypertensive Rats |
title |
The Peripheral Serotonergic System and Platelet Aggregation in Cyclosporin A-Induced Hypertensive Rats |
spellingShingle |
The Peripheral Serotonergic System and Platelet Aggregation in Cyclosporin A-Induced Hypertensive Rats Reis, Flávio Cyclosporin A Hypertension Thromboembolic complications Serotonin Aggregation |
title_short |
The Peripheral Serotonergic System and Platelet Aggregation in Cyclosporin A-Induced Hypertensive Rats |
title_full |
The Peripheral Serotonergic System and Platelet Aggregation in Cyclosporin A-Induced Hypertensive Rats |
title_fullStr |
The Peripheral Serotonergic System and Platelet Aggregation in Cyclosporin A-Induced Hypertensive Rats |
title_full_unstemmed |
The Peripheral Serotonergic System and Platelet Aggregation in Cyclosporin A-Induced Hypertensive Rats |
title_sort |
The Peripheral Serotonergic System and Platelet Aggregation in Cyclosporin A-Induced Hypertensive Rats |
author |
Reis, Flávio |
author_facet |
Reis, Flávio Tavares, Paula Ribeiro, C. A. Fontes Antunes, Ferrer Teixeira, Frederico |
author_role |
author |
author2 |
Tavares, Paula Ribeiro, C. A. Fontes Antunes, Ferrer Teixeira, Frederico |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Reis, Flávio Tavares, Paula Ribeiro, C. A. Fontes Antunes, Ferrer Teixeira, Frederico |
dc.subject.por.fl_str_mv |
Cyclosporin A Hypertension Thromboembolic complications Serotonin Aggregation |
topic |
Cyclosporin A Hypertension Thromboembolic complications Serotonin Aggregation |
description |
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. |
publishDate |
1999 |
dc.date.none.fl_str_mv |
1999 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/4844 http://hdl.handle.net/10316/4844 https://doi.org/10.1016/S0049-3848(99)00115-2 |
url |
http://hdl.handle.net/10316/4844 https://doi.org/10.1016/S0049-3848(99)00115-2 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Thrombosis Research. 96:5 (1999) 365-372 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
aplication/PDF |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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