Cardiovascular protective effects of nebivolol in Zucker diabetic fatty rats

Autores
Toblli, Jorge Eduardo; Cao, Gabriel Fernando; Rivas, Carlos Francisco; Muñoz, Marina Cecilia; Giani, Jorge Fernando; Dominici, Fernando Pablo; Angerosa, Margarita
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
BACKGROUND: Although effective in reducing blood pressure, therapy with a first-generation [beta]-blocker is currently controversial in metabolic syndrome due to its negative impact on carbohydrate and lipid metabolism. OBJECTIVE AND DESIGN: We evaluated the effects of nebivolol, a third-generation highly selective [beta]-blocker with additional vasodilating activity, versus the traditional [beta]-blocker atenolol in controlling functional and morphological cardiovascular damage in a rat model of metabolic syndrome. METHODS: During 6 months, Zucker diabetic fatty (ZDF) rats and control lean Zucker rats (LZR) were studied. The experimental groups were: untreated ZDF, ZDF along with nebivolol, ZDF along with atenolol and LZR. Blood pressure, plasma insulin, triglycerides, cholesterol, glucose and platelet aggregation were evaluated. Malondialdehyde, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, CuZn superoxide dismutase, catalase and glutathione peroxidase were determined in heart homogenates and transforming growth factor [beta]1 and plasminogen activator inhibitor-1 (PAI-1) expression, by immunohistochemistry (IHC). Vascular reactivity, vascular cell adhesion molecule-1, platelet endothelial cell adhesion molecule-1, PAI-1, enhanced nitric oxide synthase and collagen expression were evaluated in aorta. RESULTS: Nebivolol and atenolol presented a similar reduction in blood pressure. However, nebivolol showed a better lipid profile, preserved left ventricular function, a significant control in left ventricular geometry and moderated left ventricular hypertrophy versus atenolol. Significant reduction in platelet aggregation and a substantial endothelium-dependent and endothelium-independent relaxation in vessels were also shown in the nebivolol group versus atenolol group. Antioxidant defenses were preserved by nebivolol with a reduction in oxidative stress parameters. Vascular cell adhesion molecule-1, platelet endothelial cell adhesion molecule-1, PAI-1 and eNOS were favorably modulated with nebivolol in vessel wall. TGF[beta]1, PAI-1 and accumulation of collagen-III and collagen-I were also diminished in heart with nebivolol. CONCLUSION: The present study provides substantial information supporting an actual protective role of nebivolol in comparison with atenolol in experimental metabolic syndrome.
Fil: Toblli, Jorge Eduardo. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cao, Gabriel Fernando. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rivas, Carlos Francisco. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Muñoz, Marina Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Giani, Jorge Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Dominici, Fernando Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Angerosa, Margarita. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina
Materia
Aorta
Beta Blockers
Metabolic Syndrome
Zucker Diabetic Fatty Rats
Heart
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/18227
Acceder
id CONICETDig_29878693dc6e7723b9f4045ffe8a1ba3
oai_identifier_str oai:ri.conicet.gov.ar:11336/18227
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cardiovascular protective effects of nebivolol in Zucker diabetic fatty ratsToblli, Jorge EduardoCao, Gabriel FernandoRivas, Carlos FranciscoMuñoz, Marina CeciliaGiani, Jorge FernandoDominici, Fernando PabloAngerosa, MargaritaAortaBeta BlockersMetabolic SyndromeZucker Diabetic Fatty RatsHearthttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3BACKGROUND: Although effective in reducing blood pressure, therapy with a first-generation [beta]-blocker is currently controversial in metabolic syndrome due to its negative impact on carbohydrate and lipid metabolism. OBJECTIVE AND DESIGN: We evaluated the effects of nebivolol, a third-generation highly selective [beta]-blocker with additional vasodilating activity, versus the traditional [beta]-blocker atenolol in controlling functional and morphological cardiovascular damage in a rat model of metabolic syndrome. METHODS: During 6 months, Zucker diabetic fatty (ZDF) rats and control lean Zucker rats (LZR) were studied. The experimental groups were: untreated ZDF, ZDF along with nebivolol, ZDF along with atenolol and LZR. Blood pressure, plasma insulin, triglycerides, cholesterol, glucose and platelet aggregation were evaluated. Malondialdehyde, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, CuZn superoxide dismutase, catalase and glutathione peroxidase were determined in heart homogenates and transforming growth factor [beta]1 and plasminogen activator inhibitor-1 (PAI-1) expression, by immunohistochemistry (IHC). Vascular reactivity, vascular cell adhesion molecule-1, platelet endothelial cell adhesion molecule-1, PAI-1, enhanced nitric oxide synthase and collagen expression were evaluated in aorta. RESULTS: Nebivolol and atenolol presented a similar reduction in blood pressure. However, nebivolol showed a better lipid profile, preserved left ventricular function, a significant control in left ventricular geometry and moderated left ventricular hypertrophy versus atenolol. Significant reduction in platelet aggregation and a substantial endothelium-dependent and endothelium-independent relaxation in vessels were also shown in the nebivolol group versus atenolol group. Antioxidant defenses were preserved by nebivolol with a reduction in oxidative stress parameters. Vascular cell adhesion molecule-1, platelet endothelial cell adhesion molecule-1, PAI-1 and eNOS were favorably modulated with nebivolol in vessel wall. TGF[beta]1, PAI-1 and accumulation of collagen-III and collagen-I were also diminished in heart with nebivolol. CONCLUSION: The present study provides substantial information supporting an actual protective role of nebivolol in comparison with atenolol in experimental metabolic syndrome.Fil: Toblli, Jorge Eduardo. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cao, Gabriel Fernando. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rivas, Carlos Francisco. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Muñoz, Marina Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Giani, Jorge Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Dominici, Fernando Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Angerosa, Margarita. Hospital Alemán. Laboratorio de Medicina Experimental; ArgentinaLippincott Williams2010-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/18227Toblli, Jorge Eduardo; Cao, Gabriel Fernando; Rivas, Carlos Francisco; Muñoz, Marina Cecilia; Giani, Jorge Fernando; et al.; Cardiovascular protective effects of nebivolol in Zucker diabetic fatty rats; Lippincott Williams; Journal of Hypertension; 28; 5; 5-2010; 1007-10190263-6352CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1097/HJH.0b013e328337598cinfo:eu-repo/semantics/altIdentifier/url/http://journals.lww.com/jhypertension/pages/articleviewer.aspx?year=2010&issue=05000&article=00020&type=abstractinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:08:23Zoai:ri.conicet.gov.ar:11336/18227instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:08:24.022CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cardiovascular protective effects of nebivolol in Zucker diabetic fatty rats
title Cardiovascular protective effects of nebivolol in Zucker diabetic fatty rats
spellingShingle Cardiovascular protective effects of nebivolol in Zucker diabetic fatty rats
Toblli, Jorge Eduardo
Aorta
Beta Blockers
Metabolic Syndrome
Zucker Diabetic Fatty Rats
Heart
title_short Cardiovascular protective effects of nebivolol in Zucker diabetic fatty rats
title_full Cardiovascular protective effects of nebivolol in Zucker diabetic fatty rats
title_fullStr Cardiovascular protective effects of nebivolol in Zucker diabetic fatty rats
title_full_unstemmed Cardiovascular protective effects of nebivolol in Zucker diabetic fatty rats
title_sort Cardiovascular protective effects of nebivolol in Zucker diabetic fatty rats
dc.creator.none.fl_str_mv Toblli, Jorge Eduardo
Cao, Gabriel Fernando
Rivas, Carlos Francisco
Muñoz, Marina Cecilia
Giani, Jorge Fernando
Dominici, Fernando Pablo
Angerosa, Margarita
author Toblli, Jorge Eduardo
author_facet Toblli, Jorge Eduardo
Cao, Gabriel Fernando
Rivas, Carlos Francisco
Muñoz, Marina Cecilia
Giani, Jorge Fernando
Dominici, Fernando Pablo
Angerosa, Margarita
author_role author
author2 Cao, Gabriel Fernando
Rivas, Carlos Francisco
Muñoz, Marina Cecilia
Giani, Jorge Fernando
Dominici, Fernando Pablo
Angerosa, Margarita
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Aorta
Beta Blockers
Metabolic Syndrome
Zucker Diabetic Fatty Rats
Heart
topic Aorta
Beta Blockers
Metabolic Syndrome
Zucker Diabetic Fatty Rats
Heart
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv BACKGROUND: Although effective in reducing blood pressure, therapy with a first-generation [beta]-blocker is currently controversial in metabolic syndrome due to its negative impact on carbohydrate and lipid metabolism. OBJECTIVE AND DESIGN: We evaluated the effects of nebivolol, a third-generation highly selective [beta]-blocker with additional vasodilating activity, versus the traditional [beta]-blocker atenolol in controlling functional and morphological cardiovascular damage in a rat model of metabolic syndrome. METHODS: During 6 months, Zucker diabetic fatty (ZDF) rats and control lean Zucker rats (LZR) were studied. The experimental groups were: untreated ZDF, ZDF along with nebivolol, ZDF along with atenolol and LZR. Blood pressure, plasma insulin, triglycerides, cholesterol, glucose and platelet aggregation were evaluated. Malondialdehyde, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, CuZn superoxide dismutase, catalase and glutathione peroxidase were determined in heart homogenates and transforming growth factor [beta]1 and plasminogen activator inhibitor-1 (PAI-1) expression, by immunohistochemistry (IHC). Vascular reactivity, vascular cell adhesion molecule-1, platelet endothelial cell adhesion molecule-1, PAI-1, enhanced nitric oxide synthase and collagen expression were evaluated in aorta. RESULTS: Nebivolol and atenolol presented a similar reduction in blood pressure. However, nebivolol showed a better lipid profile, preserved left ventricular function, a significant control in left ventricular geometry and moderated left ventricular hypertrophy versus atenolol. Significant reduction in platelet aggregation and a substantial endothelium-dependent and endothelium-independent relaxation in vessels were also shown in the nebivolol group versus atenolol group. Antioxidant defenses were preserved by nebivolol with a reduction in oxidative stress parameters. Vascular cell adhesion molecule-1, platelet endothelial cell adhesion molecule-1, PAI-1 and eNOS were favorably modulated with nebivolol in vessel wall. TGF[beta]1, PAI-1 and accumulation of collagen-III and collagen-I were also diminished in heart with nebivolol. CONCLUSION: The present study provides substantial information supporting an actual protective role of nebivolol in comparison with atenolol in experimental metabolic syndrome.
Fil: Toblli, Jorge Eduardo. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cao, Gabriel Fernando. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rivas, Carlos Francisco. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Muñoz, Marina Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Giani, Jorge Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Dominici, Fernando Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Angerosa, Margarita. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina
description BACKGROUND: Although effective in reducing blood pressure, therapy with a first-generation [beta]-blocker is currently controversial in metabolic syndrome due to its negative impact on carbohydrate and lipid metabolism. OBJECTIVE AND DESIGN: We evaluated the effects of nebivolol, a third-generation highly selective [beta]-blocker with additional vasodilating activity, versus the traditional [beta]-blocker atenolol in controlling functional and morphological cardiovascular damage in a rat model of metabolic syndrome. METHODS: During 6 months, Zucker diabetic fatty (ZDF) rats and control lean Zucker rats (LZR) were studied. The experimental groups were: untreated ZDF, ZDF along with nebivolol, ZDF along with atenolol and LZR. Blood pressure, plasma insulin, triglycerides, cholesterol, glucose and platelet aggregation were evaluated. Malondialdehyde, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, CuZn superoxide dismutase, catalase and glutathione peroxidase were determined in heart homogenates and transforming growth factor [beta]1 and plasminogen activator inhibitor-1 (PAI-1) expression, by immunohistochemistry (IHC). Vascular reactivity, vascular cell adhesion molecule-1, platelet endothelial cell adhesion molecule-1, PAI-1, enhanced nitric oxide synthase and collagen expression were evaluated in aorta. RESULTS: Nebivolol and atenolol presented a similar reduction in blood pressure. However, nebivolol showed a better lipid profile, preserved left ventricular function, a significant control in left ventricular geometry and moderated left ventricular hypertrophy versus atenolol. Significant reduction in platelet aggregation and a substantial endothelium-dependent and endothelium-independent relaxation in vessels were also shown in the nebivolol group versus atenolol group. Antioxidant defenses were preserved by nebivolol with a reduction in oxidative stress parameters. Vascular cell adhesion molecule-1, platelet endothelial cell adhesion molecule-1, PAI-1 and eNOS were favorably modulated with nebivolol in vessel wall. TGF[beta]1, PAI-1 and accumulation of collagen-III and collagen-I were also diminished in heart with nebivolol. CONCLUSION: The present study provides substantial information supporting an actual protective role of nebivolol in comparison with atenolol in experimental metabolic syndrome.
publishDate 2010
dc.date.none.fl_str_mv 2010-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/18227
Toblli, Jorge Eduardo; Cao, Gabriel Fernando; Rivas, Carlos Francisco; Muñoz, Marina Cecilia; Giani, Jorge Fernando; et al.; Cardiovascular protective effects of nebivolol in Zucker diabetic fatty rats; Lippincott Williams; Journal of Hypertension; 28; 5; 5-2010; 1007-1019
0263-6352
CONICET Digital
CONICET
url http://hdl.handle.net/11336/18227
identifier_str_mv Toblli, Jorge Eduardo; Cao, Gabriel Fernando; Rivas, Carlos Francisco; Muñoz, Marina Cecilia; Giani, Jorge Fernando; et al.; Cardiovascular protective effects of nebivolol in Zucker diabetic fatty rats; Lippincott Williams; Journal of Hypertension; 28; 5; 5-2010; 1007-1019
0263-6352
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1097/HJH.0b013e328337598c
info:eu-repo/semantics/altIdentifier/url/http://journals.lww.com/jhypertension/pages/articleviewer.aspx?year=2010&issue=05000&article=00020&type=abstract
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
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dc.publisher.none.fl_str_mv Lippincott Williams
publisher.none.fl_str_mv Lippincott Williams
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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