A carboximetil-glucana exerce ação anti-hipertensiva, modulação positiva da função vascular e atividade antiplaquetária em ratos espontaneamente hipertensos

Detalhes bibliográficos
Autor(a) principal: Bezerra, Lorena Soares
Data de Publicação: 2021
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFPB
Texto Completo: https://repositorio.ufpb.br/jspui/handle/123456789/22516
Resumo: Yeast β-D-Glucans are polysaccharides consisting of a central linear skeleton of glucose units linked at the β (1-3) position and side chains joined by β (1-6) linkages. These polymers are important biological response modifiers and have several biological effects beneficial to health. Therefore, there is great interest in its derivatives, especially in the carboxymethylated form, which demonstrates antioxidant, immunostimulant, antiplatelet, and vascular function modulating action. However, its action on cardiovascular function is still poorly understood, mainly in hypertension. Therefore, this study aimed to investigate the effects of Carboxymethyl-glucan (CMG) from Saccharomyces cerevisiae on blood pressure, vascular function, autonomic modulation, platelet aggregation, and oxidative stress in spontaneously hypertensive rats (SHR). All experimental protocols were approved by the UFPB's Ethics Committee on Animal Use (CEUA 087/2017). Male SHR and their normotensive Wistar Kyoto (WKY) controls were assigned to groups (n=8): WKY control (WKY CT); WKY CMG 60 mg/kg; SHR control (SHR CT); SHR CMG 20 mg/kg and SHR CMG 60 mg/kg. The animals were treated for four weeks at doses of 20 and 60 mg/kg orally, and the controls received saline. At the end of treatment, weight gain, biochemical parameters, blood pressure levels, baroreflex sensitivity, and sympathetic tone participation were evaluated. Then, the animals were euthanized for vascular reactivity tests, platelet aggregation evaluation, histological, morphometric, and antioxidant capacity analyses. The results showed that CMG treatment decreased the weight gain in SHR CMG 60 mg/kg, and changed lipid profile and renal function, with a reduction in urea. Only in the SHR CMG 60 mg/kg group was observed a significant reduction in mean arterial pressure. However, the two doses tested promoted a reduction in systolic and diastolic blood pressure, without changing heart rate in the SHR groups, and also decreased cardiac hypertrophy.Modulation in baroreflex gain was observed, promoting improved response in SHR CMG 60 mg/kg animals, and decreased sympathetic tone involvement in this group. As for vascular function, improvement in the endothelium dependent vasorelaxant response assessed by acetylcholine (ACh) was verified in SHR CMG 20 mg/kg and SHR CMG 60 mg/kg groups. In the vasorelaxation induced by sodium nitroprusside (SPN), an improved response was observed in the WKY CMG 60 mg/kg animals. Platelet aggregation studies demonstrated lower platelet aggregation in the SHR CMG 60 mg/kg group compared to the SHR CT, when induced by adenosine diphosphate (ADP). Oxidative stress analyses showed that although SHR CT animals had significantly higher levels of reactive oxygen species (ROS) compared to WKY CT, CMG was not able to promote ROS reduction. These findings suggest that CMG improves vascular function in SHR animals, demonstrating antihypertensive action through baroreflex via negative modulation of sympathetic tone, and has platelet antiaggregant property. Thus, CMG presents itself as a potential strategy for the management of arterial hypertension.
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spelling A carboximetil-glucana exerce ação anti-hipertensiva, modulação positiva da função vascular e atividade antiplaquetária em ratos espontaneamente hipertensosβ-D-GlucanaCarboximetilglucanaHipertensãoBarorreflexoPlaquetasβ-D-GlucanCarboxymethyl-glucanHypertensionBaroreflexPlateletCNPQ::CIENCIAS DA SAUDE::NUTRICAOYeast β-D-Glucans are polysaccharides consisting of a central linear skeleton of glucose units linked at the β (1-3) position and side chains joined by β (1-6) linkages. These polymers are important biological response modifiers and have several biological effects beneficial to health. Therefore, there is great interest in its derivatives, especially in the carboxymethylated form, which demonstrates antioxidant, immunostimulant, antiplatelet, and vascular function modulating action. However, its action on cardiovascular function is still poorly understood, mainly in hypertension. Therefore, this study aimed to investigate the effects of Carboxymethyl-glucan (CMG) from Saccharomyces cerevisiae on blood pressure, vascular function, autonomic modulation, platelet aggregation, and oxidative stress in spontaneously hypertensive rats (SHR). All experimental protocols were approved by the UFPB's Ethics Committee on Animal Use (CEUA 087/2017). Male SHR and their normotensive Wistar Kyoto (WKY) controls were assigned to groups (n=8): WKY control (WKY CT); WKY CMG 60 mg/kg; SHR control (SHR CT); SHR CMG 20 mg/kg and SHR CMG 60 mg/kg. The animals were treated for four weeks at doses of 20 and 60 mg/kg orally, and the controls received saline. At the end of treatment, weight gain, biochemical parameters, blood pressure levels, baroreflex sensitivity, and sympathetic tone participation were evaluated. Then, the animals were euthanized for vascular reactivity tests, platelet aggregation evaluation, histological, morphometric, and antioxidant capacity analyses. The results showed that CMG treatment decreased the weight gain in SHR CMG 60 mg/kg, and changed lipid profile and renal function, with a reduction in urea. Only in the SHR CMG 60 mg/kg group was observed a significant reduction in mean arterial pressure. However, the two doses tested promoted a reduction in systolic and diastolic blood pressure, without changing heart rate in the SHR groups, and also decreased cardiac hypertrophy.Modulation in baroreflex gain was observed, promoting improved response in SHR CMG 60 mg/kg animals, and decreased sympathetic tone involvement in this group. As for vascular function, improvement in the endothelium dependent vasorelaxant response assessed by acetylcholine (ACh) was verified in SHR CMG 20 mg/kg and SHR CMG 60 mg/kg groups. In the vasorelaxation induced by sodium nitroprusside (SPN), an improved response was observed in the WKY CMG 60 mg/kg animals. Platelet aggregation studies demonstrated lower platelet aggregation in the SHR CMG 60 mg/kg group compared to the SHR CT, when induced by adenosine diphosphate (ADP). Oxidative stress analyses showed that although SHR CT animals had significantly higher levels of reactive oxygen species (ROS) compared to WKY CT, CMG was not able to promote ROS reduction. These findings suggest that CMG improves vascular function in SHR animals, demonstrating antihypertensive action through baroreflex via negative modulation of sympathetic tone, and has platelet antiaggregant property. Thus, CMG presents itself as a potential strategy for the management of arterial hypertension.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESFundação de Apoio à Pesquisa do Estado da Paraíba - FAPESQAs β-D-Glucanas de levedura são polissacarídios constituídos por um esqueleto linear central de unidades de glicose ligadas na posição β (1-3) e cadeias laterais unidas por ligações β (1-6). Esses polímeros são importantes modificadores de resposta biológica e possuem diversos efeitos biológicos benéficos a saúde. Por isso, há grande interesse em seus derivados, principalmente na forma carboximetilada, que demonstra ação antioxidante, imunoestimulante, antiplaquetária e moduladora da função vascular. Entretanto, sua ação sobre a função cardiovascular ainda é pouco compreendida, principalmente na hipertensão. Diante disso, o estudo buscou investigar quais os efeitos da Carboximetil-glucana (CMG) da Saccharomyces cerevisiae sobre a pressão arterial, função vascular, modulação autonômica, atividade plaquetária e estresse oxidativo em animais espontaneamente hipertensos (SHR). Todos os protocolos experimentais foram aprovados pelo Comitê de Ética no Uso de Animais da UFPB (CEUA 087/2017) Ratos machos SHR e seus controles normotensos Wistar Kyoto (WKY) foram distribuídos em grupos (n=8): WKY controle (WKY CT); WKY CMG 60 mg/kg; SHR controle (SHR CT); SHR CMG 20 mg/kg e SHR CMG 60 mg/kg. Os animais foram tratados durante quatro semanas nas doses de 20 e 60 mg/kg por via oral, e os controles receberam solução salina. Ao final do tratamento, foram avaliados o ganho de peso, parâmetros bioquímicos, os níveis pressóricos, a sensibilidade do barorreflexo e a participação do tônus simpático. Em seguida, os animais foram eutanasiados para testes de reatividade vascular, avaliação da agregação plaquetária, análises histológica, morfométrica e da capacidade antioxidante. Os resultados mostraram que o tratamento com CMG reduziu o ganho de peso no grupo SHR CMG 60 mg/kg, alterou o perfil lipídico e a função renal, com redução na ureia. Apenas no grupo SHR CMG 60 mg/kg foi observado redução significativa na pressão arterial média. No entanto, as duas doses testadas promoveram redução na pressão arterial sistólica e diastólica, sem alterar a frequência cardíaca nos grupos SHR, e ainda diminuiu a hipertrofia cardíaca. Foi observado modulação no ganho do barorreflexo, promovendo melhora na resposta dos animais SHR CMG 60 mg/kg, e diminuição na participação do tônus simpático nesse grupo. Quanto à função vascular, foi constatada melhora na resposta vasorrelaxante dependente de endotélio avaliada pela acetilcolina (ACh) nos grupos SHR CMG 20 mg/kg e SHR CMG 60 mg/kg. No vasorrelaxamento induzido pelo nitroprussiato de sódio (NPS), observou-se melhora na resposta no grupo WKY CMG 60 mg/kg. Os estudos de agregação plaquetária demonstraram menor agregação plaquetária no grupo SHR CMG 60 mg/Kg em relação ao SHR CT quando induzido por difosfato de adenosina (ADP). As análises de estresse oxidativo mostraram que, apesar de os animais SHR CT apresentarem significativamente maiores níveis de espécies reativas de oxigênio (ROS) comparados aos WKY CT, a CMG não foi capaz de promover a redução de ROS. Esses achados sugerem que a CMG melhora a função vascular de animais SHR, demonstrando ação anti-hipertensiva através do barorreflexo via modulação negativa do tônus simpático, e possui propriedade antiagregante plaquetária. Assim, a CMG se apresenta como potencial estratégia para o manejo da hipertensão arterial.Universidade Federal da ParaíbaBrasilCiências da NutriçãoPrograma de Pós-Graduação em Ciências da NutriçãoUFPBVeras, Robson Cavalcantehttp://lattes.cnpq.br/7217783998192557Bezerra, Lorena Soares2022-03-24T19:42:05Z2021-11-092022-03-24T19:42:05Z2021-10-29info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesishttps://repositorio.ufpb.br/jspui/handle/123456789/22516porAttribution-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nd/3.0/br/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2022-04-05T17:33:10Zoai:repositorio.ufpb.br:123456789/22516Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2022-04-05T17:33:10Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false
dc.title.none.fl_str_mv A carboximetil-glucana exerce ação anti-hipertensiva, modulação positiva da função vascular e atividade antiplaquetária em ratos espontaneamente hipertensos
title A carboximetil-glucana exerce ação anti-hipertensiva, modulação positiva da função vascular e atividade antiplaquetária em ratos espontaneamente hipertensos
spellingShingle A carboximetil-glucana exerce ação anti-hipertensiva, modulação positiva da função vascular e atividade antiplaquetária em ratos espontaneamente hipertensos
Bezerra, Lorena Soares
β-D-Glucana
Carboximetilglucana
Hipertensão
Barorreflexo
Plaquetas
β-D-Glucan
Carboxymethyl-glucan
Hypertension
Baroreflex
Platelet
CNPQ::CIENCIAS DA SAUDE::NUTRICAO
title_short A carboximetil-glucana exerce ação anti-hipertensiva, modulação positiva da função vascular e atividade antiplaquetária em ratos espontaneamente hipertensos
title_full A carboximetil-glucana exerce ação anti-hipertensiva, modulação positiva da função vascular e atividade antiplaquetária em ratos espontaneamente hipertensos
title_fullStr A carboximetil-glucana exerce ação anti-hipertensiva, modulação positiva da função vascular e atividade antiplaquetária em ratos espontaneamente hipertensos
title_full_unstemmed A carboximetil-glucana exerce ação anti-hipertensiva, modulação positiva da função vascular e atividade antiplaquetária em ratos espontaneamente hipertensos
title_sort A carboximetil-glucana exerce ação anti-hipertensiva, modulação positiva da função vascular e atividade antiplaquetária em ratos espontaneamente hipertensos
author Bezerra, Lorena Soares
author_facet Bezerra, Lorena Soares
author_role author
dc.contributor.none.fl_str_mv Veras, Robson Cavalcante
http://lattes.cnpq.br/7217783998192557
dc.contributor.author.fl_str_mv Bezerra, Lorena Soares
dc.subject.por.fl_str_mv β-D-Glucana
Carboximetilglucana
Hipertensão
Barorreflexo
Plaquetas
β-D-Glucan
Carboxymethyl-glucan
Hypertension
Baroreflex
Platelet
CNPQ::CIENCIAS DA SAUDE::NUTRICAO
topic β-D-Glucana
Carboximetilglucana
Hipertensão
Barorreflexo
Plaquetas
β-D-Glucan
Carboxymethyl-glucan
Hypertension
Baroreflex
Platelet
CNPQ::CIENCIAS DA SAUDE::NUTRICAO
description Yeast β-D-Glucans are polysaccharides consisting of a central linear skeleton of glucose units linked at the β (1-3) position and side chains joined by β (1-6) linkages. These polymers are important biological response modifiers and have several biological effects beneficial to health. Therefore, there is great interest in its derivatives, especially in the carboxymethylated form, which demonstrates antioxidant, immunostimulant, antiplatelet, and vascular function modulating action. However, its action on cardiovascular function is still poorly understood, mainly in hypertension. Therefore, this study aimed to investigate the effects of Carboxymethyl-glucan (CMG) from Saccharomyces cerevisiae on blood pressure, vascular function, autonomic modulation, platelet aggregation, and oxidative stress in spontaneously hypertensive rats (SHR). All experimental protocols were approved by the UFPB's Ethics Committee on Animal Use (CEUA 087/2017). Male SHR and their normotensive Wistar Kyoto (WKY) controls were assigned to groups (n=8): WKY control (WKY CT); WKY CMG 60 mg/kg; SHR control (SHR CT); SHR CMG 20 mg/kg and SHR CMG 60 mg/kg. The animals were treated for four weeks at doses of 20 and 60 mg/kg orally, and the controls received saline. At the end of treatment, weight gain, biochemical parameters, blood pressure levels, baroreflex sensitivity, and sympathetic tone participation were evaluated. Then, the animals were euthanized for vascular reactivity tests, platelet aggregation evaluation, histological, morphometric, and antioxidant capacity analyses. The results showed that CMG treatment decreased the weight gain in SHR CMG 60 mg/kg, and changed lipid profile and renal function, with a reduction in urea. Only in the SHR CMG 60 mg/kg group was observed a significant reduction in mean arterial pressure. However, the two doses tested promoted a reduction in systolic and diastolic blood pressure, without changing heart rate in the SHR groups, and also decreased cardiac hypertrophy.Modulation in baroreflex gain was observed, promoting improved response in SHR CMG 60 mg/kg animals, and decreased sympathetic tone involvement in this group. As for vascular function, improvement in the endothelium dependent vasorelaxant response assessed by acetylcholine (ACh) was verified in SHR CMG 20 mg/kg and SHR CMG 60 mg/kg groups. In the vasorelaxation induced by sodium nitroprusside (SPN), an improved response was observed in the WKY CMG 60 mg/kg animals. Platelet aggregation studies demonstrated lower platelet aggregation in the SHR CMG 60 mg/kg group compared to the SHR CT, when induced by adenosine diphosphate (ADP). Oxidative stress analyses showed that although SHR CT animals had significantly higher levels of reactive oxygen species (ROS) compared to WKY CT, CMG was not able to promote ROS reduction. These findings suggest that CMG improves vascular function in SHR animals, demonstrating antihypertensive action through baroreflex via negative modulation of sympathetic tone, and has platelet antiaggregant property. Thus, CMG presents itself as a potential strategy for the management of arterial hypertension.
publishDate 2021
dc.date.none.fl_str_mv 2021-11-09
2021-10-29
2022-03-24T19:42:05Z
2022-03-24T19:42:05Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://repositorio.ufpb.br/jspui/handle/123456789/22516
url https://repositorio.ufpb.br/jspui/handle/123456789/22516
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv Attribution-NoDerivs 3.0 Brazil
http://creativecommons.org/licenses/by-nd/3.0/br/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NoDerivs 3.0 Brazil
http://creativecommons.org/licenses/by-nd/3.0/br/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Universidade Federal da Paraíba
Brasil
Ciências da Nutrição
Programa de Pós-Graduação em Ciências da Nutrição
UFPB
publisher.none.fl_str_mv Universidade Federal da Paraíba
Brasil
Ciências da Nutrição
Programa de Pós-Graduação em Ciências da Nutrição
UFPB
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da UFPB
instname:Universidade Federal da Paraíba (UFPB)
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reponame_str Biblioteca Digital de Teses e Dissertações da UFPB
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repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)
repository.mail.fl_str_mv diretoria@ufpb.br|| diretoria@ufpb.br
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