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Estudo do papel do sistema purinérgico na mediação das respostas cardiovasculares do núcleo ambíguo e do reflexo bezold-jarisch em ratos anestesiados

Detalhes bibliográficos
Ano de defesa: 2009
Autor(a) principal: Passamani, Luciana Mesquita
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:
NA
ATP
612
Link de acesso: http://repositorio.ufes.br/handle/10/7923
Resumo: The purine nucleotide adenosine 5’-triphosphate (ATP) may act as a neurotransmitter/neuromodulator in the central nervous system, including nuclei associated with autonomic control. Anatomical studies have demonstrated the existence of P2 receptors in the nucleus ambiguus (NA). However, very little is known about the role of these receptors in mediating the cardiovascular responses of the NA. Therefore, the aims of our study were: a) to evaluate the effects on blood pressure and heart rate of the activation of purinoceptors in the NA, b) to evaluate the effects of the autonomic blockade on the cardiovascular responses due to the activation of purinoceptors in the NA, c) to evaluate if the purinoceptors modulate the cardiovascular responses due to glutamatergic activation of the NA, and d) to evaluate the role of the purinergic system at the level of the NA in mediating the cardiovascular responses of the Bezold-Jarish reflex. This study used anesthetized (urethane, 1.4 g/kg, i.p.) Wistar rats blocked with succinylcholine and artificially ventilated. The femoral artery and vein were catheterized to allow cardiovascular recordings and drugs injections, respectively. The stereotaxic coordinates used to reach the NA were: +0.5 mm rostral to obex, ±1.7 mm lateral and -1.2 to -1.8 mm ventral. The following drugs were used: L-Glutamate (5.0 nmol/50 nL), ATP (0.31; 2.5; 3.5; 5.0; 6.0 nmol/50 nL), prazosin (1.0 mg/kg), methyl-atropine (2.0 mg/kg), PPADS (500 pmol/100 nL) and saline (0.9%). The Bezold-Jarish reflex was activated by the intravenous injection of phenylbiguanide (12.0 µg/kg). Our data showed dosedependent bradycardic responses and also pressor responses to the ATP microinjection in the NA with the doses tested (0.31; 2.5; 3.5; 5.0; 6.0 nmol/50 nL). The α1-adrenergic blockade with prazosin did not change the bradycardic response but abolished the pressor response to the ATP (3.5 nmol/50 nL) microinjection in the NA. The muscarinic blockade with methyl-atropine abolished the bradycardic response induced by the ATP (3.5 nmol/50 nL). Ipsilateral microinjection of PPADS (500 pmol/100 nL) in the NA significantly attenuated the bradycardia but did not affect the pressor response to the ATP (3.5 nmol/50 nL) in the NA. Moreover, ipsilateral microinjection of PPADS (500 pmol/100 nL) in the NA significantly attenuated the bradicardic response to LGlutamate (5.0 nmol/50 nL) microinjection into the NA. Bilateral microinjections of PPADS in the NA significantly attenuated the depressor and bradycardic responses due to the Bezold-Jarisch reflex activation. These results suggest that the P2 purinoceptors seem to be involved in the mediation of the cardiovagal responses of the NA and that this effect might involve a neuromodulation of the glutamatergic system at the level of the NA in anesthetized rats. Additionally, our data show that the purinoceptors of the NA, seem to participate in the mediation of the cardiovascular responses of the Bezold-Jarish reflex. However, the specific subtypes of purinergic receptors involved in these responses as well as the participation of the purinergic system in other cardiovascular reflexes at the level of the NA, remain to be elucidated.
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spelling Estudo do papel do sistema purinérgico na mediação das respostas cardiovasculares do núcleo ambíguo e do reflexo bezold-jarisch em ratos anestesiadosP2 purinergic receptorsBezold-Jarisch reflexNANúcleo ambíguoReceptores purinérgicos P2ATPPPADSReflexo Bezold-JarischFisiologia612The purine nucleotide adenosine 5’-triphosphate (ATP) may act as a neurotransmitter/neuromodulator in the central nervous system, including nuclei associated with autonomic control. Anatomical studies have demonstrated the existence of P2 receptors in the nucleus ambiguus (NA). However, very little is known about the role of these receptors in mediating the cardiovascular responses of the NA. Therefore, the aims of our study were: a) to evaluate the effects on blood pressure and heart rate of the activation of purinoceptors in the NA, b) to evaluate the effects of the autonomic blockade on the cardiovascular responses due to the activation of purinoceptors in the NA, c) to evaluate if the purinoceptors modulate the cardiovascular responses due to glutamatergic activation of the NA, and d) to evaluate the role of the purinergic system at the level of the NA in mediating the cardiovascular responses of the Bezold-Jarish reflex. This study used anesthetized (urethane, 1.4 g/kg, i.p.) Wistar rats blocked with succinylcholine and artificially ventilated. The femoral artery and vein were catheterized to allow cardiovascular recordings and drugs injections, respectively. The stereotaxic coordinates used to reach the NA were: +0.5 mm rostral to obex, ±1.7 mm lateral and -1.2 to -1.8 mm ventral. The following drugs were used: L-Glutamate (5.0 nmol/50 nL), ATP (0.31; 2.5; 3.5; 5.0; 6.0 nmol/50 nL), prazosin (1.0 mg/kg), methyl-atropine (2.0 mg/kg), PPADS (500 pmol/100 nL) and saline (0.9%). The Bezold-Jarish reflex was activated by the intravenous injection of phenylbiguanide (12.0 µg/kg). Our data showed dosedependent bradycardic responses and also pressor responses to the ATP microinjection in the NA with the doses tested (0.31; 2.5; 3.5; 5.0; 6.0 nmol/50 nL). The α1-adrenergic blockade with prazosin did not change the bradycardic response but abolished the pressor response to the ATP (3.5 nmol/50 nL) microinjection in the NA. The muscarinic blockade with methyl-atropine abolished the bradycardic response induced by the ATP (3.5 nmol/50 nL). Ipsilateral microinjection of PPADS (500 pmol/100 nL) in the NA significantly attenuated the bradycardia but did not affect the pressor response to the ATP (3.5 nmol/50 nL) in the NA. Moreover, ipsilateral microinjection of PPADS (500 pmol/100 nL) in the NA significantly attenuated the bradicardic response to LGlutamate (5.0 nmol/50 nL) microinjection into the NA. Bilateral microinjections of PPADS in the NA significantly attenuated the depressor and bradycardic responses due to the Bezold-Jarisch reflex activation. These results suggest that the P2 purinoceptors seem to be involved in the mediation of the cardiovagal responses of the NA and that this effect might involve a neuromodulation of the glutamatergic system at the level of the NA in anesthetized rats. Additionally, our data show that the purinoceptors of the NA, seem to participate in the mediation of the cardiovascular responses of the Bezold-Jarish reflex. However, the specific subtypes of purinergic receptors involved in these responses as well as the participation of the purinergic system in other cardiovascular reflexes at the level of the NA, remain to be elucidated.O nucleotídeo purinérgico, adenosina 5-trifosfato (ATP) pode agir como um neurotransmissor/neuromodulador no sistema nervoso central, inclusive em núcleos associados com o controle autonômico. Estudos anatômicos têm demonstrado a existência de receptores purinérgicos P2 no núcleo ambíguo (NA). Entretanto, pouco se sabe sobre o papel desses receptores na mediação das respostas cardiovasculares do NA. Sendo assim, o nosso trabalho teve como objetivos: a) avaliar os efeitos da ativação dos receptores purinérgicos do NA sobre a pressão arterial e a frequência cardíaca, b) avaliar os efeitos do bloqueio autonômico periférico na modulação das respostas cardiovasculares mediadas pela ativação dos receptores purinérgicos do NA, c) avaliar o papel dos receptores purinérgicos na modulação das respostas mediadas pela ativação glutamatérgica do NA, e d) avaliar a modulação do sistema purinérgico ao nível do NA na mediação das respostas cardiovasculares do reflexo Bezold-Jarisch. Foram utilizados ratos Wistar, anestesiados com uretana (1,4 g/kg, i.p.), paralisados com succinilcolina e ventilados artificialmente. A artéria e veia femorais foram cateterizadas para permitir os registros cardiovasculares e a administração de drogas, respectivamente. As coordenadas estereotáxicas de referência utilizadas para atingir o NA foram: +0,5 mm rostral ao óbex, ±1,7 mm lateral e -1,2 a -1,8 mm ventral. As drogas utilizadas foram: L-Glutamato (5,0 nmol/50 nL), ATP (0,31; 2,5; 3,5; 5,0; 6,0 nmol/50 nL), prazosin (1,0 mg/kg), metil-atropina (2,0 mg/kg), PPADS (500 pmol/100 nL) e solução salina (0,9%). O reflexo Bezold-Jarisch foi ativado pela administração intravenosa de fenilbiguanida (12,0 µg/kg). Os dados obtidos mostraram respostas bradicárdicas com um padrão dose-dependente e também respostas pressoras às microinjeções de ATP nas doses testadas (0,31; 2,5; 3,5; 5,0; 6,0 nmol/50 nL) no NA. O bloqueio α1-adrenérgico com prazosin não alterou significativamente a resposta bradicárdica, mas aboliu a resposta pressora gerada pela microinjeção de ATP (3,5 nmol/50 nL). O bloqueio muscarínico com metil-atropina aboliu a resposta bradicárdica gerada pela microinjeção de ATP (3,5 nmol/50 nL). Microinjeções ipsilaterais de PPADS (500 pmol/100 nL) no NA promoveram uma significativa atenuação da resposta bradicárdica e nenhuma alteração na resposta pressora à microinjeção de ATP no NA (3,5 nmol/50 nL). Além disso, microinjeções ipsilaterais de PPADS (500 pmol/100 nL) no NA promoveram uma significativa atenuação da resposta bradicárdica gerada pela microinjeção de L-Glutamato (5,0 nmol/50 nL). Microinjeções bilaterais de PPADS (500 pmol/100 nL) no NA atenuaram significativamente as respostas hipotensora e bradicárdica do reflexo Bezold-Jarisch. Estes resultados sugerem que os receptores purinérgicos do tipo P2 no NA parecem estar envolvidos na mediação das respostas cardiovagais ao ATP e que estes efeitos podem envolver uma neuromodulação do sistema glutamatérgico ao nível do NA em ratos anestesiados. Adicionalmente, nossos dados mostram que os receptores purinérgicos do tipo P2 do NA, parecem ter participação na mediação das respostas cardiovasculares do reflexo Bezold-Jarisch. No entanto, os subtipos específicos de receptores purinérgicos envolvidos bem como a participação do sistema purinérgico em outros reflexos cardiovasculares ao nível do NA permanecem por ser elucidados.Universidade Federal do Espírito SantoBRMestrado em Ciências FisiológicasCentro de Ciências da SaúdeUFESPrograma de Pós-Graduação em Ciências FisiológicasSampaio, Karla NíveaSchenberg, Luiz CarlosMauad, HélderMachado, Benedito HonórioPassamani, Luciana Mesquita2018-08-01T22:58:31Z2018-08-012018-08-01T22:58:31Z2009-03-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisTextapplication/pdfhttp://repositorio.ufes.br/handle/10/7923porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)instname:Universidade Federal do Espírito Santo (UFES)instacron:UFES2024-07-16T17:07:56Zoai:repositorio.ufes.br:10/7923Repositório InstitucionalPUBhttp://repositorio.ufes.br/oai/requestriufes@ufes.bropendoar:21082024-07-16T17:07:56Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) - Universidade Federal do Espírito Santo (UFES)false
dc.title.none.fl_str_mv Estudo do papel do sistema purinérgico na mediação das respostas cardiovasculares do núcleo ambíguo e do reflexo bezold-jarisch em ratos anestesiados
title Estudo do papel do sistema purinérgico na mediação das respostas cardiovasculares do núcleo ambíguo e do reflexo bezold-jarisch em ratos anestesiados
spellingShingle Estudo do papel do sistema purinérgico na mediação das respostas cardiovasculares do núcleo ambíguo e do reflexo bezold-jarisch em ratos anestesiados
Passamani, Luciana Mesquita
P2 purinergic receptors
Bezold-Jarisch reflex
NA
Núcleo ambíguo
Receptores purinérgicos P2
ATP
PPADS
Reflexo Bezold-Jarisch
Fisiologia
612
title_short Estudo do papel do sistema purinérgico na mediação das respostas cardiovasculares do núcleo ambíguo e do reflexo bezold-jarisch em ratos anestesiados
title_full Estudo do papel do sistema purinérgico na mediação das respostas cardiovasculares do núcleo ambíguo e do reflexo bezold-jarisch em ratos anestesiados
title_fullStr Estudo do papel do sistema purinérgico na mediação das respostas cardiovasculares do núcleo ambíguo e do reflexo bezold-jarisch em ratos anestesiados
title_full_unstemmed Estudo do papel do sistema purinérgico na mediação das respostas cardiovasculares do núcleo ambíguo e do reflexo bezold-jarisch em ratos anestesiados
title_sort Estudo do papel do sistema purinérgico na mediação das respostas cardiovasculares do núcleo ambíguo e do reflexo bezold-jarisch em ratos anestesiados
author Passamani, Luciana Mesquita
author_facet Passamani, Luciana Mesquita
author_role author
dc.contributor.none.fl_str_mv Sampaio, Karla Nívea
Schenberg, Luiz Carlos
Mauad, Hélder
Machado, Benedito Honório
dc.contributor.author.fl_str_mv Passamani, Luciana Mesquita
dc.subject.por.fl_str_mv P2 purinergic receptors
Bezold-Jarisch reflex
NA
Núcleo ambíguo
Receptores purinérgicos P2
ATP
PPADS
Reflexo Bezold-Jarisch
Fisiologia
612
topic P2 purinergic receptors
Bezold-Jarisch reflex
NA
Núcleo ambíguo
Receptores purinérgicos P2
ATP
PPADS
Reflexo Bezold-Jarisch
Fisiologia
612
description The purine nucleotide adenosine 5’-triphosphate (ATP) may act as a neurotransmitter/neuromodulator in the central nervous system, including nuclei associated with autonomic control. Anatomical studies have demonstrated the existence of P2 receptors in the nucleus ambiguus (NA). However, very little is known about the role of these receptors in mediating the cardiovascular responses of the NA. Therefore, the aims of our study were: a) to evaluate the effects on blood pressure and heart rate of the activation of purinoceptors in the NA, b) to evaluate the effects of the autonomic blockade on the cardiovascular responses due to the activation of purinoceptors in the NA, c) to evaluate if the purinoceptors modulate the cardiovascular responses due to glutamatergic activation of the NA, and d) to evaluate the role of the purinergic system at the level of the NA in mediating the cardiovascular responses of the Bezold-Jarish reflex. This study used anesthetized (urethane, 1.4 g/kg, i.p.) Wistar rats blocked with succinylcholine and artificially ventilated. The femoral artery and vein were catheterized to allow cardiovascular recordings and drugs injections, respectively. The stereotaxic coordinates used to reach the NA were: +0.5 mm rostral to obex, ±1.7 mm lateral and -1.2 to -1.8 mm ventral. The following drugs were used: L-Glutamate (5.0 nmol/50 nL), ATP (0.31; 2.5; 3.5; 5.0; 6.0 nmol/50 nL), prazosin (1.0 mg/kg), methyl-atropine (2.0 mg/kg), PPADS (500 pmol/100 nL) and saline (0.9%). The Bezold-Jarish reflex was activated by the intravenous injection of phenylbiguanide (12.0 µg/kg). Our data showed dosedependent bradycardic responses and also pressor responses to the ATP microinjection in the NA with the doses tested (0.31; 2.5; 3.5; 5.0; 6.0 nmol/50 nL). The α1-adrenergic blockade with prazosin did not change the bradycardic response but abolished the pressor response to the ATP (3.5 nmol/50 nL) microinjection in the NA. The muscarinic blockade with methyl-atropine abolished the bradycardic response induced by the ATP (3.5 nmol/50 nL). Ipsilateral microinjection of PPADS (500 pmol/100 nL) in the NA significantly attenuated the bradycardia but did not affect the pressor response to the ATP (3.5 nmol/50 nL) in the NA. Moreover, ipsilateral microinjection of PPADS (500 pmol/100 nL) in the NA significantly attenuated the bradicardic response to LGlutamate (5.0 nmol/50 nL) microinjection into the NA. Bilateral microinjections of PPADS in the NA significantly attenuated the depressor and bradycardic responses due to the Bezold-Jarisch reflex activation. These results suggest that the P2 purinoceptors seem to be involved in the mediation of the cardiovagal responses of the NA and that this effect might involve a neuromodulation of the glutamatergic system at the level of the NA in anesthetized rats. Additionally, our data show that the purinoceptors of the NA, seem to participate in the mediation of the cardiovascular responses of the Bezold-Jarish reflex. However, the specific subtypes of purinergic receptors involved in these responses as well as the participation of the purinergic system in other cardiovascular reflexes at the level of the NA, remain to be elucidated.
publishDate 2009
dc.date.none.fl_str_mv 2009-03-01
2018-08-01T22:58:31Z
2018-08-01
2018-08-01T22:58:31Z
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/10/7923
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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)
instacron:UFES
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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