Enantioselective pharmacokinetics and cardiovascular effects of nebivolol in L-NAME hypertensive rats

Autores
Bertera, Facundo Martin; del Mauro, Julieta Sofía; Lovera, Valeria; Chiappetta, Diego Andrés; Polizio, Ariel Héctor; Taira, Carlos Alberto; Höcht, Christian
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The cardiovascular effects and pharmacokinetics of nebivolol were assessed in N(G)-nitro-l-arginine methyl ester (L-NAME) hypertensive and normotensive control rats. Male Wistar rats were randomly divided to drink tap water (control) or L-NAME solution for 2 weeks. The effects of nebivolol (3 or 10 mg kg−1 i.v.) on blood pressure (BP), heart rate and BP variability (BPV) were recorded in awake L-NAME and control rats. Short-term and beat-to-beat BPV was assessed by the s.d. and spectral analysis of the BP recordings. Nebivolol pharmacokinetics was studied by means of traditional blood sampling. Nebivolol showed enantioselective pharmacokinetics in both experimental groups; the clearance and the volume of distribution of l-nebivolol were significantly greater than those of the d-enantiomer. The hypotensive response to nebivolol was significantly enhanced in L-NAME rats (Δmean arterial pressure (MAP): −16.1±1.1%, P<0.05 vs. control rats) compared with normotensive animals (ΔMAP: −1.4±2.1%). An analysis of the beat-to-beat BPV showed a greater reduction in VLF BPV in the L-NAME compare with the control rats. Nebivolol significantly reduced the low-frequency/high-frequency ratio in hypertensive L-NAME animals compared with normotensive rats. Short-term BPV was markedly reduced by nebivolol in both experimental groups, although the attenuation of the s.d. of BP recording was greater in L-NAME rats. In conclusion, the hypotensive efficacy of nebivolol is significantly enhanced in L-NAME rats compared with normotensive animals, which is most likely due to a greater reduction in vascular sympathetic activity. Nebivolol markedly attenuated short-term BPV in both experimental groups, suggesting that β-blockers with additional pharmacological actions provide beneficial cardiovascular effects by controlling high BP and its short-term variability.
Fil: Bertera, Facundo Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: del Mauro, Julieta Sofía. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Lovera, Valeria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Chiappetta, Diego Andrés. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Polizio, Ariel Héctor. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Taira, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Materia
Blood Pressure Variability
Enantioselective Pharmacokinetics
L-Name Hypertension
Nebivolol
Spectral Analysis
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:11336/18124
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/18124
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Enantioselective pharmacokinetics and cardiovascular effects of nebivolol in L-NAME hypertensive ratsBertera, Facundo Martindel Mauro, Julieta SofíaLovera, ValeriaChiappetta, Diego AndrésPolizio, Ariel HéctorTaira, Carlos AlbertoHöcht, ChristianBlood Pressure VariabilityEnantioselective PharmacokineticsL-Name HypertensionNebivololSpectral Analysishttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The cardiovascular effects and pharmacokinetics of nebivolol were assessed in N(G)-nitro-l-arginine methyl ester (L-NAME) hypertensive and normotensive control rats. Male Wistar rats were randomly divided to drink tap water (control) or L-NAME solution for 2 weeks. The effects of nebivolol (3 or 10 mg kg−1 i.v.) on blood pressure (BP), heart rate and BP variability (BPV) were recorded in awake L-NAME and control rats. Short-term and beat-to-beat BPV was assessed by the s.d. and spectral analysis of the BP recordings. Nebivolol pharmacokinetics was studied by means of traditional blood sampling. Nebivolol showed enantioselective pharmacokinetics in both experimental groups; the clearance and the volume of distribution of l-nebivolol were significantly greater than those of the d-enantiomer. The hypotensive response to nebivolol was significantly enhanced in L-NAME rats (Δmean arterial pressure (MAP): −16.1±1.1%, P<0.05 vs. control rats) compared with normotensive animals (ΔMAP: −1.4±2.1%). An analysis of the beat-to-beat BPV showed a greater reduction in VLF BPV in the L-NAME compare with the control rats. Nebivolol significantly reduced the low-frequency/high-frequency ratio in hypertensive L-NAME animals compared with normotensive rats. Short-term BPV was markedly reduced by nebivolol in both experimental groups, although the attenuation of the s.d. of BP recording was greater in L-NAME rats. In conclusion, the hypotensive efficacy of nebivolol is significantly enhanced in L-NAME rats compared with normotensive animals, which is most likely due to a greater reduction in vascular sympathetic activity. Nebivolol markedly attenuated short-term BPV in both experimental groups, suggesting that β-blockers with additional pharmacological actions provide beneficial cardiovascular effects by controlling high BP and its short-term variability.Fil: Bertera, Facundo Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; ArgentinaFil: del Mauro, Julieta Sofía. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; ArgentinaFil: Lovera, Valeria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; ArgentinaFil: Chiappetta, Diego Andrés. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Polizio, Ariel Héctor. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Taira, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; ArgentinaNature Publishing Group2014-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/18124Bertera, Facundo Martin; del Mauro, Julieta Sofía; Lovera, Valeria; Chiappetta, Diego Andrés; Polizio, Ariel Héctor; et al.; Enantioselective pharmacokinetics and cardiovascular effects of nebivolol in L-NAME hypertensive rats; Nature Publishing Group; Hypertension Research; 37; 3; 3-2014; 194-2010916-9636enginfo:eu-repo/semantics/altIdentifier/url/http://www.nature.com/hr/journal/v37/n3/full/hr2013140a.htmlinfo:eu-repo/semantics/altIdentifier/doi/10.1038/hr.2013.140info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:54:48Zoai:ri.conicet.gov.ar:11336/18124instacron: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 09:54:49.286CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Enantioselective pharmacokinetics and cardiovascular effects of nebivolol in L-NAME hypertensive rats
title Enantioselective pharmacokinetics and cardiovascular effects of nebivolol in L-NAME hypertensive rats
spellingShingle Enantioselective pharmacokinetics and cardiovascular effects of nebivolol in L-NAME hypertensive rats
Bertera, Facundo Martin
Blood Pressure Variability
Enantioselective Pharmacokinetics
L-Name Hypertension
Nebivolol
Spectral Analysis
title_short Enantioselective pharmacokinetics and cardiovascular effects of nebivolol in L-NAME hypertensive rats
title_full Enantioselective pharmacokinetics and cardiovascular effects of nebivolol in L-NAME hypertensive rats
title_fullStr Enantioselective pharmacokinetics and cardiovascular effects of nebivolol in L-NAME hypertensive rats
title_full_unstemmed Enantioselective pharmacokinetics and cardiovascular effects of nebivolol in L-NAME hypertensive rats
title_sort Enantioselective pharmacokinetics and cardiovascular effects of nebivolol in L-NAME hypertensive rats
dc.creator.none.fl_str_mv Bertera, Facundo Martin
del Mauro, Julieta Sofía
Lovera, Valeria
Chiappetta, Diego Andrés
Polizio, Ariel Héctor
Taira, Carlos Alberto
Höcht, Christian
author Bertera, Facundo Martin
author_facet Bertera, Facundo Martin
del Mauro, Julieta Sofía
Lovera, Valeria
Chiappetta, Diego Andrés
Polizio, Ariel Héctor
Taira, Carlos Alberto
Höcht, Christian
author_role author
author2 del Mauro, Julieta Sofía
Lovera, Valeria
Chiappetta, Diego Andrés
Polizio, Ariel Héctor
Taira, Carlos Alberto
Höcht, Christian
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Blood Pressure Variability
Enantioselective Pharmacokinetics
L-Name Hypertension
Nebivolol
Spectral Analysis
topic Blood Pressure Variability
Enantioselective Pharmacokinetics
L-Name Hypertension
Nebivolol
Spectral Analysis
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The cardiovascular effects and pharmacokinetics of nebivolol were assessed in N(G)-nitro-l-arginine methyl ester (L-NAME) hypertensive and normotensive control rats. Male Wistar rats were randomly divided to drink tap water (control) or L-NAME solution for 2 weeks. The effects of nebivolol (3 or 10 mg kg−1 i.v.) on blood pressure (BP), heart rate and BP variability (BPV) were recorded in awake L-NAME and control rats. Short-term and beat-to-beat BPV was assessed by the s.d. and spectral analysis of the BP recordings. Nebivolol pharmacokinetics was studied by means of traditional blood sampling. Nebivolol showed enantioselective pharmacokinetics in both experimental groups; the clearance and the volume of distribution of l-nebivolol were significantly greater than those of the d-enantiomer. The hypotensive response to nebivolol was significantly enhanced in L-NAME rats (Δmean arterial pressure (MAP): −16.1±1.1%, P<0.05 vs. control rats) compared with normotensive animals (ΔMAP: −1.4±2.1%). An analysis of the beat-to-beat BPV showed a greater reduction in VLF BPV in the L-NAME compare with the control rats. Nebivolol significantly reduced the low-frequency/high-frequency ratio in hypertensive L-NAME animals compared with normotensive rats. Short-term BPV was markedly reduced by nebivolol in both experimental groups, although the attenuation of the s.d. of BP recording was greater in L-NAME rats. In conclusion, the hypotensive efficacy of nebivolol is significantly enhanced in L-NAME rats compared with normotensive animals, which is most likely due to a greater reduction in vascular sympathetic activity. Nebivolol markedly attenuated short-term BPV in both experimental groups, suggesting that β-blockers with additional pharmacological actions provide beneficial cardiovascular effects by controlling high BP and its short-term variability.
Fil: Bertera, Facundo Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: del Mauro, Julieta Sofía. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Lovera, Valeria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Chiappetta, Diego Andrés. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Polizio, Ariel Héctor. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Taira, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
description The cardiovascular effects and pharmacokinetics of nebivolol were assessed in N(G)-nitro-l-arginine methyl ester (L-NAME) hypertensive and normotensive control rats. Male Wistar rats were randomly divided to drink tap water (control) or L-NAME solution for 2 weeks. The effects of nebivolol (3 or 10 mg kg−1 i.v.) on blood pressure (BP), heart rate and BP variability (BPV) were recorded in awake L-NAME and control rats. Short-term and beat-to-beat BPV was assessed by the s.d. and spectral analysis of the BP recordings. Nebivolol pharmacokinetics was studied by means of traditional blood sampling. Nebivolol showed enantioselective pharmacokinetics in both experimental groups; the clearance and the volume of distribution of l-nebivolol were significantly greater than those of the d-enantiomer. The hypotensive response to nebivolol was significantly enhanced in L-NAME rats (Δmean arterial pressure (MAP): −16.1±1.1%, P<0.05 vs. control rats) compared with normotensive animals (ΔMAP: −1.4±2.1%). An analysis of the beat-to-beat BPV showed a greater reduction in VLF BPV in the L-NAME compare with the control rats. Nebivolol significantly reduced the low-frequency/high-frequency ratio in hypertensive L-NAME animals compared with normotensive rats. Short-term BPV was markedly reduced by nebivolol in both experimental groups, although the attenuation of the s.d. of BP recording was greater in L-NAME rats. In conclusion, the hypotensive efficacy of nebivolol is significantly enhanced in L-NAME rats compared with normotensive animals, which is most likely due to a greater reduction in vascular sympathetic activity. Nebivolol markedly attenuated short-term BPV in both experimental groups, suggesting that β-blockers with additional pharmacological actions provide beneficial cardiovascular effects by controlling high BP and its short-term variability.
publishDate 2014
dc.date.none.fl_str_mv 2014-03
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/11336/18124
Bertera, Facundo Martin; del Mauro, Julieta Sofía; Lovera, Valeria; Chiappetta, Diego Andrés; Polizio, Ariel Héctor; et al.; Enantioselective pharmacokinetics and cardiovascular effects of nebivolol in L-NAME hypertensive rats; Nature Publishing Group; Hypertension Research; 37; 3; 3-2014; 194-201
0916-9636
url http://hdl.handle.net/11336/18124
identifier_str_mv Bertera, Facundo Martin; del Mauro, Julieta Sofía; Lovera, Valeria; Chiappetta, Diego Andrés; Polizio, Ariel Héctor; et al.; Enantioselective pharmacokinetics and cardiovascular effects of nebivolol in L-NAME hypertensive rats; Nature Publishing Group; Hypertension Research; 37; 3; 3-2014; 194-201
0916-9636
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.nature.com/hr/journal/v37/n3/full/hr2013140a.html
info:eu-repo/semantics/altIdentifier/doi/10.1038/hr.2013.140
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
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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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