Endothelium modulates contractile response to simvastatin in rat aorta

Simvastatin is an inhibitor of HMG-CoA reductase used in the treatment of hypercholesterolemia. In the present study simvastatin-induced contraction was observed in rat aortic thoracic rings, this effect increased when the endothelium was removed and when NO synthase was blocked by L-NOARG (3 x 10-5...

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Detalhes bibliográficos
Autores: Pérez Guerrero, María Concepción, Álvarez de Sotomayor Paz, María, Herrera González, María Dolores, Marhuenda Requena, Elisa
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2000
País:España
Recursos:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/96711
Acesso em linha:https://hdl.handle.net/11441/96711
https://doi.org/10.1515/znc-2000-1-222
Access Level:acceso abierto
Palavra-chave:Endothelium
HMG-CoA Reductase
Rat Aorta
Simvastatin
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spelling Endothelium modulates contractile response to simvastatin in rat aortaPérez Guerrero, María ConcepciónÁlvarez de Sotomayor Paz, MaríaHerrera González, María DoloresMarhuenda Requena, ElisaEndotheliumHMG-CoA ReductaseRat AortaSimvastatinSimvastatin is an inhibitor of HMG-CoA reductase used in the treatment of hypercholesterolemia. In the present study simvastatin-induced contraction was observed in rat aortic thoracic rings, this effect increased when the endothelium was removed and when NO synthase was blocked by L-NOARG (3 x 10-5 M). The contractile effect of simvastatin on intact aortic rings diminished when cyclo-oxygenase was inhibited with indomethacin (10-5 M). Also in the presence of endothelium, pretreatment with mevalonate (1 mM), the product of HMGCoA reductase activity, significantly inhibited the contraction. In other experiments carried out on endothelium-removed preparations and in medium containing the calcium antagonist, diltiazem (10-5 and 10-6 M), the contraction dose-response curves were significantly reduced and the same happened in the presence of the inhibitor of sarcoplasmic reticulum Ca-2+ATPase, cyclopiazonic acid (CPA) (3 x 10-6 M). The results suggest that simvastatin might increase intracellular calcium concentration. This effect could lead to an activation of NO synthase and cyclooxygenase pathways in endothelial cells and to contraction in vascular smooth muscle cells. This rise in Ca2+ concentration could be due to an inhibition of isoprenoid synthesis prevented by mevalonate.Walter de GruyterFarmacología2000info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/96711https://doi.org/10.1515/znc-2000-1-222reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésZeitschrift fur Naturforschung - Section C Journal of Biosciences, 55 (1-2), 121-124.http://dx.doi.org/10.1515/znc-2000-1-222info:eu-repo/semantics/openAccessoai:idus.us.es:11441/967112026-06-17T12:51:07Z
dc.title.none.fl_str_mv Endothelium modulates contractile response to simvastatin in rat aorta
title Endothelium modulates contractile response to simvastatin in rat aorta
spellingShingle Endothelium modulates contractile response to simvastatin in rat aorta
Pérez Guerrero, María Concepción
Endothelium
HMG-CoA Reductase
Rat Aorta
Simvastatin
title_short Endothelium modulates contractile response to simvastatin in rat aorta
title_full Endothelium modulates contractile response to simvastatin in rat aorta
title_fullStr Endothelium modulates contractile response to simvastatin in rat aorta
title_full_unstemmed Endothelium modulates contractile response to simvastatin in rat aorta
title_sort Endothelium modulates contractile response to simvastatin in rat aorta
dc.creator.none.fl_str_mv Pérez Guerrero, María Concepción
Álvarez de Sotomayor Paz, María
Herrera González, María Dolores
Marhuenda Requena, Elisa
author Pérez Guerrero, María Concepción
author_facet Pérez Guerrero, María Concepción
Álvarez de Sotomayor Paz, María
Herrera González, María Dolores
Marhuenda Requena, Elisa
author_role author
author2 Álvarez de Sotomayor Paz, María
Herrera González, María Dolores
Marhuenda Requena, Elisa
author2_role author
author
author
dc.contributor.none.fl_str_mv Farmacología
dc.subject.none.fl_str_mv Endothelium
HMG-CoA Reductase
Rat Aorta
Simvastatin
topic Endothelium
HMG-CoA Reductase
Rat Aorta
Simvastatin
description Simvastatin is an inhibitor of HMG-CoA reductase used in the treatment of hypercholesterolemia. In the present study simvastatin-induced contraction was observed in rat aortic thoracic rings, this effect increased when the endothelium was removed and when NO synthase was blocked by L-NOARG (3 x 10-5 M). The contractile effect of simvastatin on intact aortic rings diminished when cyclo-oxygenase was inhibited with indomethacin (10-5 M). Also in the presence of endothelium, pretreatment with mevalonate (1 mM), the product of HMGCoA reductase activity, significantly inhibited the contraction. In other experiments carried out on endothelium-removed preparations and in medium containing the calcium antagonist, diltiazem (10-5 and 10-6 M), the contraction dose-response curves were significantly reduced and the same happened in the presence of the inhibitor of sarcoplasmic reticulum Ca-2+ATPase, cyclopiazonic acid (CPA) (3 x 10-6 M). The results suggest that simvastatin might increase intracellular calcium concentration. This effect could lead to an activation of NO synthase and cyclooxygenase pathways in endothelial cells and to contraction in vascular smooth muscle cells. This rise in Ca2+ concentration could be due to an inhibition of isoprenoid synthesis prevented by mevalonate.
publishDate 2000
dc.date.none.fl_str_mv 2000
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/96711
https://doi.org/10.1515/znc-2000-1-222
url https://hdl.handle.net/11441/96711
https://doi.org/10.1515/znc-2000-1-222
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Zeitschrift fur Naturforschung - Section C Journal of Biosciences, 55 (1-2), 121-124.
http://dx.doi.org/10.1515/znc-2000-1-222
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Walter de Gruyter
publisher.none.fl_str_mv Walter de Gruyter
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301629

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