Efeitos cardiovasculares da exposição crônica a cloreto de mercúrio em ratos

Detalhes bibliográficos
Ano de defesa: 2008
Autor(a) principal: Furieri, Lorena Barros
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal do Espírito Santo
BR
Mestrado em Ciências Fisiológicas
Centro de Ciências da Saúde
UFES
Programa de Pós-Graduação em Ciências Fisiológicas
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
612
Link de acesso: http://repositorio.ufes.br/handle/10/5152
Resumo: The evaluation of environmental exposure to small quantities of mercury showed that the metal affects the cardiovascular system. The chronic exposition produces hypertension and correlates with cardiovascular events and promotes oxidative stress. Our objective was to study the effects of 20 nM HgCl2 exposure during 30 days on hemodynamic parameters and cardiac contractility. Wistar rats were divided at random in 2 groups. The control group received intramuscular injections (IM) of saline during 30 days and the treated group received, in the first day, one IM injection containing HgCl2 sufficient to produce a plasma concentration of 20 nM HgCl2. Until the end of the treatment period rats received a supplement dose to maintain the desired plasma concentration. After 30 days rats were anesthetized, received heparin and the right carotid artery and jugular vein were cannulate, for measurements of systolic, diastolic and mean arterial pressure, left and right systolic and diastolic ventricular pressure and their time derivatives. In isolated perfused rats according to the Langendorff technique contractile characteristics were investigated. A latex balloon, connected to a pressure transducer was used to measure isovolumetric left ventricular systolic and diastolic pressures. The following protocols were performed: progressive increments of diastolic pressure and the answer to β-adrenergic stimulation. Throughout the experiment the coronary mean perfusion pressure was measured (CPP). Cardiac contractility was also evaluated in left ventricle papillary muscles: inotropism, temporal parameters, sarcoplasmic reticulum activity, sarcolemmal calcium permeability and the role of contractile proteins. The myocardial activities of Na+ -K+ -ATPase (NKA) and myosin Ca2+ ATPase were also measured. Statistical analyses: two-way ANOVA and the Student t- test. p< 0,05 was considered significant. Hemodynamic parameters showed one single alteration, the increase of the left ventricular end diastolic pressure (LVEDP) in the Mercury group when compared to control. However, in isolated hearts it was observed in the HgCl2 group reduction of developed pressure and time derivatives in control conditions and in all diastolic pressures. The hearts from the Mercury group also showed a reduction of the βadrenergic response. Moreover, the HgCl2 chronic treatment was not capable to alter the contractile parameters in left ventricle papillary muscles, but increased the myosin Ca2+ ATPase and the NKA specific activity. Possibly the LVEDP increase in vivo and the negative inotropic effect observed in isolated hearts are linked to the NKA inhibition that causes an increase of intracellular calcium inducing a defective relaxation by the myocardium calcium overload. Considering that the hemodynamic parameters are preserved in vivo we could speculate that neuro-humoral factors might be playing a role to maintain the cardiac inotropic state and the arterial pressure. The increased activity of the myosin Ca2+ ATPase might also be a compensatory mechanism of the cardiac muscle. We suggest that the reduction of the β-adrenergic response is a consequence of a desensitization process caused by an increased sympathetic tone as a compensatory mechanism during HgCl2 exposure. We might conclude that the chronic exposure to a small concentration of HgCl2 produces a negative inotropic effect in isolated hearts, a relaxation deficit in vivo and an increase of myosin ATPase activity and NKA inhibtion.
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spelling Efeitos cardiovasculares da exposição crônica a cloreto de mercúrio em ratosMercúrioCoração isoladoMúsculo papilareContratilidade miocárdicaFisiologia612The evaluation of environmental exposure to small quantities of mercury showed that the metal affects the cardiovascular system. The chronic exposition produces hypertension and correlates with cardiovascular events and promotes oxidative stress. Our objective was to study the effects of 20 nM HgCl2 exposure during 30 days on hemodynamic parameters and cardiac contractility. Wistar rats were divided at random in 2 groups. The control group received intramuscular injections (IM) of saline during 30 days and the treated group received, in the first day, one IM injection containing HgCl2 sufficient to produce a plasma concentration of 20 nM HgCl2. Until the end of the treatment period rats received a supplement dose to maintain the desired plasma concentration. After 30 days rats were anesthetized, received heparin and the right carotid artery and jugular vein were cannulate, for measurements of systolic, diastolic and mean arterial pressure, left and right systolic and diastolic ventricular pressure and their time derivatives. In isolated perfused rats according to the Langendorff technique contractile characteristics were investigated. A latex balloon, connected to a pressure transducer was used to measure isovolumetric left ventricular systolic and diastolic pressures. The following protocols were performed: progressive increments of diastolic pressure and the answer to β-adrenergic stimulation. Throughout the experiment the coronary mean perfusion pressure was measured (CPP). Cardiac contractility was also evaluated in left ventricle papillary muscles: inotropism, temporal parameters, sarcoplasmic reticulum activity, sarcolemmal calcium permeability and the role of contractile proteins. The myocardial activities of Na+ -K+ -ATPase (NKA) and myosin Ca2+ ATPase were also measured. Statistical analyses: two-way ANOVA and the Student t- test. p< 0,05 was considered significant. Hemodynamic parameters showed one single alteration, the increase of the left ventricular end diastolic pressure (LVEDP) in the Mercury group when compared to control. However, in isolated hearts it was observed in the HgCl2 group reduction of developed pressure and time derivatives in control conditions and in all diastolic pressures. The hearts from the Mercury group also showed a reduction of the βadrenergic response. Moreover, the HgCl2 chronic treatment was not capable to alter the contractile parameters in left ventricle papillary muscles, but increased the myosin Ca2+ ATPase and the NKA specific activity. Possibly the LVEDP increase in vivo and the negative inotropic effect observed in isolated hearts are linked to the NKA inhibition that causes an increase of intracellular calcium inducing a defective relaxation by the myocardium calcium overload. Considering that the hemodynamic parameters are preserved in vivo we could speculate that neuro-humoral factors might be playing a role to maintain the cardiac inotropic state and the arterial pressure. The increased activity of the myosin Ca2+ ATPase might also be a compensatory mechanism of the cardiac muscle. We suggest that the reduction of the β-adrenergic response is a consequence of a desensitization process caused by an increased sympathetic tone as a compensatory mechanism during HgCl2 exposure. We might conclude that the chronic exposure to a small concentration of HgCl2 produces a negative inotropic effect in isolated hearts, a relaxation deficit in vivo and an increase of myosin ATPase activity and NKA inhibtion.A avaliação da exposição ambiental a pequenas quantidades de mercúrio tem demonstrado que o metal afeta o sistema cardiovascular. Sua exposição crônica promove hipertensão arterial e correlaciona-se com eventos cardiovasculares e, em baixas concentrações, promove stress oxidativo. O objetivo deste trabalho foi avaliar os efeitos da exposição por 30 dias à 20 nM de HgCl2 sobre parâmetros hemodinâmicos e a contratilidade miocárdica. Ratos Wistar foram separados aleatoriamente em dois grupos. O grupo Controle recebeu, durante 30 dias, injeções intramusculares (IM) de salina e o grupo tratado recebeu no primeiro dia de tratamento uma injeção IM de solução de HgCl2 suficiente para alcançar a concentração plasmática de 20 nM. Até o término do tratamento, os ratos recebiam diariamente doses de reforço para manter a concentração desejada. Após 30 dias os ratos eram anestesiados, heparinizados e submetidos à canulação da artéria carótida e da veia jugular direitas para medidas da pressão arterial sistólica, arterial diastólica, arterial média, e pressões sistólica e diastólica de VE e VD e suas derivadas temporais. Foram avaliados os parâmetros contráteis de corações isolados perfundidos pela técnica de Langendorff. Um balão de látex, conectado a um transdutor de pressão, foi utilizado para determinação da pressão diastólica (PD) e mensuração da pressão sistólica isovolumétrica do VE. Os protocolos realizados foram: resposta ao aumento da PD e resposta à estimulação ?-adrenérgica. Durante todo o experimento também foi medida a pressão de perfusão coronariana (PPC). Também foram analisados, em músculos papilares de VE: o inotropismo cardíaco, os parâmetros temporais, a atividade funcional do retículo arcoplasmático, a permeabilidade da membrana sarcolemal ao cálcio e a responsividade das proteínas contráteis. Por fim, foram medidas as atividades específicas da Na+-K+-ATPase (NKA) e da Ca2+ ATPase miosínica cardíacas. Análise estatística: ANOVA duas vias ou teste t-Student. p< 0,05 foi considerado significante. Os parâmetros hemodinâmicos mostraram uma única alteração, aumento da pressão diastólica final de VE (PDfVE) no grupo Mercúrio em relação ao Controle. No entanto, em corações isolados observamos, no grupo exposto ao HgCl2, diminuição da pressão desenvolvida e das derivadas temporais na condição basal e em praticamente todas as PD estudadas. Os corações do grupo Mercúrio também apresentaram diminuição da resposta ?-adrenérgica. No entanto, o tratamento crônico com HgCl2 não foi capaz de alterar os parâmetros contráteis em músculos papilares do VE, mas aumentou a atividade da e Ca2+ ATPase miosínica e inibiu a atividade específica da NKA. Possivelmente, o aumento da PDfVE in vivo e o efeito inotrópico negativo em corações isolados se devem a inibição da NKA, que causa aumento da concentração intracelular de cálcio, induzindo defeito no relaxamento por sobrecarga de cálcio no músculo cardíaco. Como os parâmetros hemodinâmicos encontram-se preservados in vivo, podemos especular que fatores neuro-humorais estejam participando da manutenção do inotropismo cardíaco e pressão arterial. O aumento da atividade da Ca2+ ATPase miosínica também poder ser um mecanismo compensatório do músculo cardíaco. Sugerimos que a diminuição da resposta ?-adrenérgica é conseqüência da dessensibilização dos receptores ? cardíacos, por uma ativação simpática aumentada, como mecanismo compensatório, durante a exposição ao HgCl2. Podemos concluir que a exposição a baixa concentração de HgCl2 promove efeito inotrópico negativo em corações isolados, déficit de relaxamento in vivo, aumento da ATPase miosina e inibição da NKA.Universidade Federal do Espírito SantoBRMestrado em Ciências FisiológicasCentro de Ciências da SaúdeUFESPrograma de Pós-Graduação em Ciências FisiológicasVassallo, Dalton ValentimStefanon, IvanitaKalinin, Ana LúciaFurieri, Lorena Barros2016-08-29T15:37:51Z2016-07-112016-08-29T15:37:51Z2008-08-14info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisTextapplication/pdfhttp://repositorio.ufes.br/handle/10/5152porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)instname:Universidade Federal do Espírito Santo (UFES)instacron:UFES2024-07-16T17:05:36Zoai:repositorio.ufes.br:10/5152Repositório InstitucionalPUBhttp://repositorio.ufes.br/oai/requestriufes@ufes.bropendoar:21082024-07-16T17:05:36Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) - Universidade Federal do Espírito Santo (UFES)false
dc.title.none.fl_str_mv Efeitos cardiovasculares da exposição crônica a cloreto de mercúrio em ratos
title Efeitos cardiovasculares da exposição crônica a cloreto de mercúrio em ratos
spellingShingle Efeitos cardiovasculares da exposição crônica a cloreto de mercúrio em ratos
Furieri, Lorena Barros
Mercúrio
Coração isolado
Músculo papilare
Contratilidade miocárdica
Fisiologia
612
title_short Efeitos cardiovasculares da exposição crônica a cloreto de mercúrio em ratos
title_full Efeitos cardiovasculares da exposição crônica a cloreto de mercúrio em ratos
title_fullStr Efeitos cardiovasculares da exposição crônica a cloreto de mercúrio em ratos
title_full_unstemmed Efeitos cardiovasculares da exposição crônica a cloreto de mercúrio em ratos
title_sort Efeitos cardiovasculares da exposição crônica a cloreto de mercúrio em ratos
author Furieri, Lorena Barros
author_facet Furieri, Lorena Barros
author_role author
dc.contributor.none.fl_str_mv Vassallo, Dalton Valentim
Stefanon, Ivanita
Kalinin, Ana Lúcia
dc.contributor.author.fl_str_mv Furieri, Lorena Barros
dc.subject.por.fl_str_mv Mercúrio
Coração isolado
Músculo papilare
Contratilidade miocárdica
Fisiologia
612
topic Mercúrio
Coração isolado
Músculo papilare
Contratilidade miocárdica
Fisiologia
612
description The evaluation of environmental exposure to small quantities of mercury showed that the metal affects the cardiovascular system. The chronic exposition produces hypertension and correlates with cardiovascular events and promotes oxidative stress. Our objective was to study the effects of 20 nM HgCl2 exposure during 30 days on hemodynamic parameters and cardiac contractility. Wistar rats were divided at random in 2 groups. The control group received intramuscular injections (IM) of saline during 30 days and the treated group received, in the first day, one IM injection containing HgCl2 sufficient to produce a plasma concentration of 20 nM HgCl2. Until the end of the treatment period rats received a supplement dose to maintain the desired plasma concentration. After 30 days rats were anesthetized, received heparin and the right carotid artery and jugular vein were cannulate, for measurements of systolic, diastolic and mean arterial pressure, left and right systolic and diastolic ventricular pressure and their time derivatives. In isolated perfused rats according to the Langendorff technique contractile characteristics were investigated. A latex balloon, connected to a pressure transducer was used to measure isovolumetric left ventricular systolic and diastolic pressures. The following protocols were performed: progressive increments of diastolic pressure and the answer to β-adrenergic stimulation. Throughout the experiment the coronary mean perfusion pressure was measured (CPP). Cardiac contractility was also evaluated in left ventricle papillary muscles: inotropism, temporal parameters, sarcoplasmic reticulum activity, sarcolemmal calcium permeability and the role of contractile proteins. The myocardial activities of Na+ -K+ -ATPase (NKA) and myosin Ca2+ ATPase were also measured. Statistical analyses: two-way ANOVA and the Student t- test. p< 0,05 was considered significant. Hemodynamic parameters showed one single alteration, the increase of the left ventricular end diastolic pressure (LVEDP) in the Mercury group when compared to control. However, in isolated hearts it was observed in the HgCl2 group reduction of developed pressure and time derivatives in control conditions and in all diastolic pressures. The hearts from the Mercury group also showed a reduction of the βadrenergic response. Moreover, the HgCl2 chronic treatment was not capable to alter the contractile parameters in left ventricle papillary muscles, but increased the myosin Ca2+ ATPase and the NKA specific activity. Possibly the LVEDP increase in vivo and the negative inotropic effect observed in isolated hearts are linked to the NKA inhibition that causes an increase of intracellular calcium inducing a defective relaxation by the myocardium calcium overload. Considering that the hemodynamic parameters are preserved in vivo we could speculate that neuro-humoral factors might be playing a role to maintain the cardiac inotropic state and the arterial pressure. The increased activity of the myosin Ca2+ ATPase might also be a compensatory mechanism of the cardiac muscle. We suggest that the reduction of the β-adrenergic response is a consequence of a desensitization process caused by an increased sympathetic tone as a compensatory mechanism during HgCl2 exposure. We might conclude that the chronic exposure to a small concentration of HgCl2 produces a negative inotropic effect in isolated hearts, a relaxation deficit in vivo and an increase of myosin ATPase activity and NKA inhibtion.
publishDate 2008
dc.date.none.fl_str_mv 2008-08-14
2016-08-29T15:37:51Z
2016-07-11
2016-08-29T15:37:51Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
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dc.identifier.uri.fl_str_mv http://repositorio.ufes.br/handle/10/5152
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dc.publisher.none.fl_str_mv Universidade Federal do Espírito Santo
BR
Mestrado em Ciências Fisiológicas
Centro de Ciências da Saúde
UFES
Programa de Pós-Graduação em Ciências Fisiológicas
publisher.none.fl_str_mv Universidade Federal do Espírito Santo
BR
Mestrado em Ciências Fisiológicas
Centro de Ciências da Saúde
UFES
Programa de Pós-Graduação em Ciências Fisiológicas
dc.source.none.fl_str_mv reponame:Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
instname:Universidade Federal do Espírito Santo (UFES)
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instname_str Universidade Federal do Espírito Santo (UFES)
instacron_str UFES
institution UFES
reponame_str Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
collection Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
repository.name.fl_str_mv Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) - Universidade Federal do Espírito Santo (UFES)
repository.mail.fl_str_mv riufes@ufes.br
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