Contribuição da neurotransmissão glutamatérgica na região rostroventrolateral do bulbo (RVLM) para as respostas cardiovasculares e autonômicas induzidas pelo fator de necrose tumoral alfa (TNF-α) no núcleo paraventricular do hipotálamo (PVN)
Ano de defesa: | 2022 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , , , , |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Goiás
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Programa de Pós-Graduação: |
Programa de Pós-graduação em Ciências Biológicas (ICB)
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Departamento: |
Instituto de Ciências Biológicas - ICB (RG)
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País: |
Brasil
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Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.bc.ufg.br/tede/handle/tede/12476 |
Resumo: | Neurogenic hypertension is characterized by a chronic elevation of blood pressure (BP) associated with exacerbation of sympathetic nerve activity (SNA). In this sense, the neuroinflammation, marked by the presence of pro-inflammatory cytokines (PIC) in the central nervous system (CNS), can be related to increased sympathetic drive and arterial hypertension (AH) development. Furthermore, the presence of tumor necrosis factor alpha (TNF-α) in sympathetic premotor neurons that compose the rostral ventrolateral medulla (RVLM) and hypothalamic paraventricular nucleus (PVN) is associated with hypertensive phenotype. However, the pathways and mechanisms by which TNF-α act in the CNS remain under investigation. Thus, the present study investigated the cardiovascular and autonomic effects promoted by TNF-α administration in the PVN and the participation of glutamatergic neurotransmission and N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the RVLM in these responses. For this, Wistar and spontaneously hypertensive rats (SHR) (270 - 300g) were anesthetized with urethane (400 mg/mL, intravenous - i.v.) associated with α-chloralose (40 mg/mL, i.v.) and instrumented to mean arterial pressure (MAP), heart rate (HR) and splanchnic sympathetic nervous activity (SSNA) recordings. The animals were organized into five groups and subjected to unilateral nanoinjections (50 nL) in the RVLM as follows: I. Wistar subjected to vehicle nanoinjections (Ringer's solution, normotensive SHAM group, n=5); II. SHR subjected to vehicle nanoinjections (Ringer's solution, hypertensive SHAM group, n=7); III. SHR subjected to kynurenic acid nanoinjections (KYN, 50 mM, glutamate receptor antagonist, hypertensive GLU group, n=6); IV. SHR subjected to 2-amino-5-phosphonovaleric acid nanoinjections (AP5, 24 nmol/50 nL, NMDA receptor antagonist, hypertensive NMDA group, n=7) and V. SHR subjected to 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f] quinoxaline nanoinjections (NBQX, 5.2 nmol/50 nL, AMPA receptor antagonist, hypertensive AMPA group, n=6). Then, all groups were subjected to ipsilateral TNF-α nanoinjections (0.6 pmol/50 nL, 50 nL) in the PVN. Nanoinjections of vehicle, KYN, AP5 or NBQX in RVLM did not change baseline values of MAP, HR and SSNA. In the normotensive SHAM group, TNF-α nanoinjections into the PVN induced an ANSE increase after 50 min of TNF-α nanoinjections, without modifying the MAP and HR. In contrast, in the hypertensive SHAM group, TNF-α nanoinjections in the PVN promoted a progressive splanchnic sympathoexcitation initiated 20 min after the TNF-α nanoinjections. After 50 min of TNF-α nanoinjections, a pressor response was observed, without changing HR, in the hypertensive SHAM group. Previous inhibition of RVLM glutamatergic neurotransmission did not alter the pressor response induced by TNF-α in hypertensive animals and did not change the HR. However, abolished the splanchnic sympathoexcitation observed after TNF-α. Additionally, NMDA or AMPA receptors previous inhibition in RVLM was not able to change the TNF-α-induced late increase in MAP and the HR in hypertensive animals. However, attenuated the splanchnic sympatoexcitation generated after the TNF-α nanoinjections. These results suggest that cardiovascular and autonomic changes promoted by TNF-α in the PVN are exacerbated in hypertensive animals and that the integrity of glutamatergic neurotransmission and NMDA and AMPA receptors in the RVLM are essential for the sympathoexcitatory response induced by TNF-α in the PVN in SHR. |
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oai:repositorio.bc.ufg.br:tede/12476 |
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Repositório Institucional da UFG |
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Pedrino, Gustavo Rodrigueshttp://lattes.cnpq.br/1155446449250341Pedrino, Gustavo RodriguesCustódio, Carlos Henrique XavierFajemiroye, James OluwagbamigbeMourão, Aline AndradeOliveira, André Henrique Freiria dehttp://lattes.cnpq.br/3584728631208203Naves, Lara Marques2022-12-13T14:32:36Z2022-12-13T14:32:36Z2022-10-31NAVES, L. M. Contribuição da neurotransmissão glutamatérgica na região rostroventrolateral do bulbo (RVLM) para as respostas cardiovasculares e autonômicas induzidas pelo fator de necrose tumoral alfa (TNF-α) no núcleo paraventricular do hipotálamo (PVN). 2022. 59 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Goiás, Goiânia, 2022.http://repositorio.bc.ufg.br/tede/handle/tede/12476Neurogenic hypertension is characterized by a chronic elevation of blood pressure (BP) associated with exacerbation of sympathetic nerve activity (SNA). In this sense, the neuroinflammation, marked by the presence of pro-inflammatory cytokines (PIC) in the central nervous system (CNS), can be related to increased sympathetic drive and arterial hypertension (AH) development. Furthermore, the presence of tumor necrosis factor alpha (TNF-α) in sympathetic premotor neurons that compose the rostral ventrolateral medulla (RVLM) and hypothalamic paraventricular nucleus (PVN) is associated with hypertensive phenotype. However, the pathways and mechanisms by which TNF-α act in the CNS remain under investigation. Thus, the present study investigated the cardiovascular and autonomic effects promoted by TNF-α administration in the PVN and the participation of glutamatergic neurotransmission and N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the RVLM in these responses. For this, Wistar and spontaneously hypertensive rats (SHR) (270 - 300g) were anesthetized with urethane (400 mg/mL, intravenous - i.v.) associated with α-chloralose (40 mg/mL, i.v.) and instrumented to mean arterial pressure (MAP), heart rate (HR) and splanchnic sympathetic nervous activity (SSNA) recordings. The animals were organized into five groups and subjected to unilateral nanoinjections (50 nL) in the RVLM as follows: I. Wistar subjected to vehicle nanoinjections (Ringer's solution, normotensive SHAM group, n=5); II. SHR subjected to vehicle nanoinjections (Ringer's solution, hypertensive SHAM group, n=7); III. SHR subjected to kynurenic acid nanoinjections (KYN, 50 mM, glutamate receptor antagonist, hypertensive GLU group, n=6); IV. SHR subjected to 2-amino-5-phosphonovaleric acid nanoinjections (AP5, 24 nmol/50 nL, NMDA receptor antagonist, hypertensive NMDA group, n=7) and V. SHR subjected to 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f] quinoxaline nanoinjections (NBQX, 5.2 nmol/50 nL, AMPA receptor antagonist, hypertensive AMPA group, n=6). Then, all groups were subjected to ipsilateral TNF-α nanoinjections (0.6 pmol/50 nL, 50 nL) in the PVN. Nanoinjections of vehicle, KYN, AP5 or NBQX in RVLM did not change baseline values of MAP, HR and SSNA. In the normotensive SHAM group, TNF-α nanoinjections into the PVN induced an ANSE increase after 50 min of TNF-α nanoinjections, without modifying the MAP and HR. In contrast, in the hypertensive SHAM group, TNF-α nanoinjections in the PVN promoted a progressive splanchnic sympathoexcitation initiated 20 min after the TNF-α nanoinjections. After 50 min of TNF-α nanoinjections, a pressor response was observed, without changing HR, in the hypertensive SHAM group. Previous inhibition of RVLM glutamatergic neurotransmission did not alter the pressor response induced by TNF-α in hypertensive animals and did not change the HR. However, abolished the splanchnic sympathoexcitation observed after TNF-α. Additionally, NMDA or AMPA receptors previous inhibition in RVLM was not able to change the TNF-α-induced late increase in MAP and the HR in hypertensive animals. However, attenuated the splanchnic sympatoexcitation generated after the TNF-α nanoinjections. These results suggest that cardiovascular and autonomic changes promoted by TNF-α in the PVN are exacerbated in hypertensive animals and that the integrity of glutamatergic neurotransmission and NMDA and AMPA receptors in the RVLM are essential for the sympathoexcitatory response induced by TNF-α in the PVN in SHR.A hipertensão neurogênica é caracterizada por uma elevação crônica da pressão arterial (PA) associada e impulsionada pela exacerbação da atividade nervosa simpática (ANS). Neste sentido, a neuroinflamação, marcada pela presença de citocinas pró-inflamatórias (CPI) no sistema nervoso central (SNC), pode estar relacionada ao aumento do tônus simpático e desenvolvimento da hipertensão arterial (HA). Ademais, a presença do fator de necrose tumoral alfa (TNF-α) nos neurônios pré-motores simpáticos que compõem a região rostroventrolateral do bulbo (RVLM) e o núcleo paraventricular do hipotálamo (PVN) está associada ao fenótipo hipertensivo. Entretanto, as vias e mecanismos pelos quais o TNF-α atua no SNC permanecem sendo investigadas. Assim, o presente estudo investigou os efeitos cardiovasculares e autonômicos promovidos pela administração de TNF-α no PVN e a participação da neurotransmissão glutamatérgica e dos receptores N-metil-D-aspartato (NMDA) e α-amino-3-hidroxi-5-metilisoxazol-4-ácido propiônico (AMPA) na região RVLM nestas respostas. Para alcançar estes objetivos, ratos Wistar e espontaneamente hipertensos (SHR) (270 - 300g) foram anestesiados com uretano (400 mg/mL, intravenoso - i.v.) associado com α-cloralose (40 mg/mL, i.v.) e instrumentalizados para registro de pressão arterial média (PAM), frequência cardíaca (FC) e atividade nervosa simpática esplâncnica (ANSE). Os animais foram organizados em cinco grupos e submetidos a nanoinjeções unilaterais (50 nL) na região RVLM conforme a seguir: I. Wistar submetidos a nanoinjeção de veículo (Solução de Ringer, grupo controle normotenso, n=5); II. SHR submetidos a nanoinjeções de veículo (Solução de Ringer, grupo controle hipertenso, n=7); III. SHR submetidos a nanoinjeções de ácido quinurênico (KYN, 50 mM, antagonista do receptor de glutamato, grupo GLU hipertenso, n=6); IV. SHR submetidos a nanoinjeções de ácido 2-amino-5-fosfonovalerico (AP5, 24 nmol/50 nL, antagonista do receptor NMDA, grupo NMDA hipertenso, n=7) e V. SHR submetidos a nanoinjeções de 2,3-di-hidroxi-6-nitro-7-sulfamoil-benzo [f] quinoxalina (NBQX, 5,2 nmol/50 nL, antagonista do receptor AMPA, grupo AMPA hipertenso, n=6). Em seguida, todos os grupos foram submetidos a nanoinjeções ipsilaterais de TNF-α (0,6 pmol/50 nL, 50 nL) no PVN. As nanoinjeções de veículo, KYN, AP5 ou NBQX na região RVLM não promoveram alterações nos valores basais da PAM, FC e ANSE. No grupo controle normotenso, as nanoinjeções de TNF-α no PVN induziram aumento da ANSE após 50 min das nanoinjeções de TNF-α, sem modificar a PAM e a FC. Em contrapartida, no grupo controle hipertenso, as nanoinjeções de TNF-α no PVN promoveram simpatoexcitação esplâncnica progressiva iniciada após 20 min das nanoinjeções de TNF-α. Após 50 min das nanoinjeções de TNF-α foi observada resposta pressora, sem alterar a FC, no grupo controle hipertenso. A inibição prévia da neurotransmissão glutamatérgica na região RVLM não alterou a resposta pressora induzida pelo TNF-α em animais hipertensos e não modificou a FC. Entretanto, aboliu a simpatoexcitação esplâncnica observada após o TNF-α. Adicionalmente, a inibição prévia dos receptores NMDA ou AMPA na região RVLM não alterou o aumento tardio da PAM e a FC induzidos pelo TNF-α em animais hipertensos. Todavia, atenuou a simpatoexcitação esplâncnica gerada após as nanoinjeções de TNF-α. Esses resultados sugerem que as alterações cardiovasculares e autonômicas promovidas pelo TNF-α no PVN são exacerbadas em animais hipertensos e que a integridade da neurotransmissão glutamatérgica e dos receptores NMDA e AMPA na região RVLM são essenciais para a resposta simpatoexcitatória induzida pelo TNF-α no PVN em SHR.Submitted by Onia Arantes Albuquerque (onia.ufg@gmail.com) on 2022-12-08T13:25:08Z No. of bitstreams: 2 Tese - Lara Marques Naves - 2022.pdf: 2884542 bytes, checksum: 8b8608ed0990ca978303b94f38b8e6f3 (MD5) license_rdf: 805 bytes, checksum: 4460e5956bc1d1639be9ae6146a50347 (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2022-12-13T14:32:35Z (GMT) No. of bitstreams: 2 Tese - Lara Marques Naves - 2022.pdf: 2884542 bytes, checksum: 8b8608ed0990ca978303b94f38b8e6f3 (MD5) license_rdf: 805 bytes, checksum: 4460e5956bc1d1639be9ae6146a50347 (MD5)Made available in DSpace on 2022-12-13T14:32:36Z (GMT). No. of bitstreams: 2 Tese - Lara Marques Naves - 2022.pdf: 2884542 bytes, checksum: 8b8608ed0990ca978303b94f38b8e6f3 (MD5) license_rdf: 805 bytes, checksum: 4460e5956bc1d1639be9ae6146a50347 (MD5) Previous issue date: 2022-10-31Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqporUniversidade Federal de GoiásPrograma de Pós-graduação em Ciências Biológicas (ICB)UFGBrasilInstituto de Ciências Biológicas - ICB (RG)Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessHipertensão arterialAtividade nervosa simpáticaInflamaçãoNeuroinflamaçãoResposta inflamatóriaArterial hypertensionSympathetic nervous activityInflammationNeuroinflammationInflammatory responseCIENCIAS BIOLOGICASContribuição da neurotransmissão glutamatérgica na região rostroventrolateral do bulbo (RVLM) para as respostas cardiovasculares e autonômicas induzidas pelo fator de necrose tumoral alfa (TNF-α) no núcleo paraventricular do hipotálamo (PVN)Contribution of glutamatergic neurotransmission in the rostral ventrolateral medulla (RVLM) to cardiovascular and autonomic responses induced by tumor necrosis factor alpha (TNF-α) in the hypothalamic paraventricular nucleus (PVN)info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis15500500500500231720reponame:Repositório Institucional da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGLICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.bc.ufg.br/tede/bitstreams/594a5d3e-a525-4bee-b8ae-470376392d65/download8a4605be74aa9ea9d79846c1fba20a33MD51ORIGINALTese - Lara Marques Naves - 2022.pdfTese - Lara Marques Naves - 2022.pdfapplication/pdf2884542http://repositorio.bc.ufg.br/tede/bitstreams/65e6fe48-ee3e-448c-8b20-ebbe031d5858/download8b8608ed0990ca978303b94f38b8e6f3MD53CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8805http://repositorio.bc.ufg.br/tede/bitstreams/a95dc0e5-39e6-44a1-aae8-19d2fe7e1245/download4460e5956bc1d1639be9ae6146a50347MD52tede/124762022-12-13 11:32:36.256http://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 Internationalopen.accessoai:repositorio.bc.ufg.br:tede/12476http://repositorio.bc.ufg.br/tedeRepositório InstitucionalPUBhttp://repositorio.bc.ufg.br/oai/requesttasesdissertacoes.bc@ufg.bropendoar:2022-12-13T14:32:36Repositório Institucional da UFG - Universidade Federal de Goiás (UFG)falseTk9URTogUExBQ0UgWU9VUiBPV04gTElDRU5TRSBIRVJFClRoaXMgc2FtcGxlIGxpY2Vuc2UgaXMgcHJvdmlkZWQgZm9yIGluZm9ybWF0aW9uYWwgcHVycG9zZXMgb25seS4KCk5PTi1FWENMVVNJVkUgRElTVFJJQlVUSU9OIExJQ0VOU0UKCkJ5IHNpZ25pbmcgYW5kIHN1Ym1pdHRpbmcgdGhpcyBsaWNlbnNlLCB5b3UgKHRoZSBhdXRob3Iocykgb3IgY29weXJpZ2h0Cm93bmVyKSBncmFudHMgdG8gRFNwYWNlIFVuaXZlcnNpdHkgKERTVSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBEU1UgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgRFNVIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgRFNVIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gRFNVLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpEU1Ugd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo= |
dc.title.pt_BR.fl_str_mv |
Contribuição da neurotransmissão glutamatérgica na região rostroventrolateral do bulbo (RVLM) para as respostas cardiovasculares e autonômicas induzidas pelo fator de necrose tumoral alfa (TNF-α) no núcleo paraventricular do hipotálamo (PVN) |
dc.title.alternative.eng.fl_str_mv |
Contribution of glutamatergic neurotransmission in the rostral ventrolateral medulla (RVLM) to cardiovascular and autonomic responses induced by tumor necrosis factor alpha (TNF-α) in the hypothalamic paraventricular nucleus (PVN) |
title |
Contribuição da neurotransmissão glutamatérgica na região rostroventrolateral do bulbo (RVLM) para as respostas cardiovasculares e autonômicas induzidas pelo fator de necrose tumoral alfa (TNF-α) no núcleo paraventricular do hipotálamo (PVN) |
spellingShingle |
Contribuição da neurotransmissão glutamatérgica na região rostroventrolateral do bulbo (RVLM) para as respostas cardiovasculares e autonômicas induzidas pelo fator de necrose tumoral alfa (TNF-α) no núcleo paraventricular do hipotálamo (PVN) Naves, Lara Marques Hipertensão arterial Atividade nervosa simpática Inflamação Neuroinflamação Resposta inflamatória Arterial hypertension Sympathetic nervous activity Inflammation Neuroinflammation Inflammatory response CIENCIAS BIOLOGICAS |
title_short |
Contribuição da neurotransmissão glutamatérgica na região rostroventrolateral do bulbo (RVLM) para as respostas cardiovasculares e autonômicas induzidas pelo fator de necrose tumoral alfa (TNF-α) no núcleo paraventricular do hipotálamo (PVN) |
title_full |
Contribuição da neurotransmissão glutamatérgica na região rostroventrolateral do bulbo (RVLM) para as respostas cardiovasculares e autonômicas induzidas pelo fator de necrose tumoral alfa (TNF-α) no núcleo paraventricular do hipotálamo (PVN) |
title_fullStr |
Contribuição da neurotransmissão glutamatérgica na região rostroventrolateral do bulbo (RVLM) para as respostas cardiovasculares e autonômicas induzidas pelo fator de necrose tumoral alfa (TNF-α) no núcleo paraventricular do hipotálamo (PVN) |
title_full_unstemmed |
Contribuição da neurotransmissão glutamatérgica na região rostroventrolateral do bulbo (RVLM) para as respostas cardiovasculares e autonômicas induzidas pelo fator de necrose tumoral alfa (TNF-α) no núcleo paraventricular do hipotálamo (PVN) |
title_sort |
Contribuição da neurotransmissão glutamatérgica na região rostroventrolateral do bulbo (RVLM) para as respostas cardiovasculares e autonômicas induzidas pelo fator de necrose tumoral alfa (TNF-α) no núcleo paraventricular do hipotálamo (PVN) |
author |
Naves, Lara Marques |
author_facet |
Naves, Lara Marques |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Pedrino, Gustavo Rodrigues |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/1155446449250341 |
dc.contributor.referee1.fl_str_mv |
Pedrino, Gustavo Rodrigues |
dc.contributor.referee2.fl_str_mv |
Custódio, Carlos Henrique Xavier |
dc.contributor.referee3.fl_str_mv |
Fajemiroye, James Oluwagbamigbe |
dc.contributor.referee4.fl_str_mv |
Mourão, Aline Andrade |
dc.contributor.referee5.fl_str_mv |
Oliveira, André Henrique Freiria de |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/3584728631208203 |
dc.contributor.author.fl_str_mv |
Naves, Lara Marques |
contributor_str_mv |
Pedrino, Gustavo Rodrigues Pedrino, Gustavo Rodrigues Custódio, Carlos Henrique Xavier Fajemiroye, James Oluwagbamigbe Mourão, Aline Andrade Oliveira, André Henrique Freiria de |
dc.subject.por.fl_str_mv |
Hipertensão arterial Atividade nervosa simpática Inflamação Neuroinflamação Resposta inflamatória |
topic |
Hipertensão arterial Atividade nervosa simpática Inflamação Neuroinflamação Resposta inflamatória Arterial hypertension Sympathetic nervous activity Inflammation Neuroinflammation Inflammatory response CIENCIAS BIOLOGICAS |
dc.subject.eng.fl_str_mv |
Arterial hypertension Sympathetic nervous activity Inflammation Neuroinflammation Inflammatory response |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS |
description |
Neurogenic hypertension is characterized by a chronic elevation of blood pressure (BP) associated with exacerbation of sympathetic nerve activity (SNA). In this sense, the neuroinflammation, marked by the presence of pro-inflammatory cytokines (PIC) in the central nervous system (CNS), can be related to increased sympathetic drive and arterial hypertension (AH) development. Furthermore, the presence of tumor necrosis factor alpha (TNF-α) in sympathetic premotor neurons that compose the rostral ventrolateral medulla (RVLM) and hypothalamic paraventricular nucleus (PVN) is associated with hypertensive phenotype. However, the pathways and mechanisms by which TNF-α act in the CNS remain under investigation. Thus, the present study investigated the cardiovascular and autonomic effects promoted by TNF-α administration in the PVN and the participation of glutamatergic neurotransmission and N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the RVLM in these responses. For this, Wistar and spontaneously hypertensive rats (SHR) (270 - 300g) were anesthetized with urethane (400 mg/mL, intravenous - i.v.) associated with α-chloralose (40 mg/mL, i.v.) and instrumented to mean arterial pressure (MAP), heart rate (HR) and splanchnic sympathetic nervous activity (SSNA) recordings. The animals were organized into five groups and subjected to unilateral nanoinjections (50 nL) in the RVLM as follows: I. Wistar subjected to vehicle nanoinjections (Ringer's solution, normotensive SHAM group, n=5); II. SHR subjected to vehicle nanoinjections (Ringer's solution, hypertensive SHAM group, n=7); III. SHR subjected to kynurenic acid nanoinjections (KYN, 50 mM, glutamate receptor antagonist, hypertensive GLU group, n=6); IV. SHR subjected to 2-amino-5-phosphonovaleric acid nanoinjections (AP5, 24 nmol/50 nL, NMDA receptor antagonist, hypertensive NMDA group, n=7) and V. SHR subjected to 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f] quinoxaline nanoinjections (NBQX, 5.2 nmol/50 nL, AMPA receptor antagonist, hypertensive AMPA group, n=6). Then, all groups were subjected to ipsilateral TNF-α nanoinjections (0.6 pmol/50 nL, 50 nL) in the PVN. Nanoinjections of vehicle, KYN, AP5 or NBQX in RVLM did not change baseline values of MAP, HR and SSNA. In the normotensive SHAM group, TNF-α nanoinjections into the PVN induced an ANSE increase after 50 min of TNF-α nanoinjections, without modifying the MAP and HR. In contrast, in the hypertensive SHAM group, TNF-α nanoinjections in the PVN promoted a progressive splanchnic sympathoexcitation initiated 20 min after the TNF-α nanoinjections. After 50 min of TNF-α nanoinjections, a pressor response was observed, without changing HR, in the hypertensive SHAM group. Previous inhibition of RVLM glutamatergic neurotransmission did not alter the pressor response induced by TNF-α in hypertensive animals and did not change the HR. However, abolished the splanchnic sympathoexcitation observed after TNF-α. Additionally, NMDA or AMPA receptors previous inhibition in RVLM was not able to change the TNF-α-induced late increase in MAP and the HR in hypertensive animals. However, attenuated the splanchnic sympatoexcitation generated after the TNF-α nanoinjections. These results suggest that cardiovascular and autonomic changes promoted by TNF-α in the PVN are exacerbated in hypertensive animals and that the integrity of glutamatergic neurotransmission and NMDA and AMPA receptors in the RVLM are essential for the sympathoexcitatory response induced by TNF-α in the PVN in SHR. |
publishDate |
2022 |
dc.date.accessioned.fl_str_mv |
2022-12-13T14:32:36Z |
dc.date.available.fl_str_mv |
2022-12-13T14:32:36Z |
dc.date.issued.fl_str_mv |
2022-10-31 |
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.citation.fl_str_mv |
NAVES, L. M. Contribuição da neurotransmissão glutamatérgica na região rostroventrolateral do bulbo (RVLM) para as respostas cardiovasculares e autonômicas induzidas pelo fator de necrose tumoral alfa (TNF-α) no núcleo paraventricular do hipotálamo (PVN). 2022. 59 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Goiás, Goiânia, 2022. |
dc.identifier.uri.fl_str_mv |
http://repositorio.bc.ufg.br/tede/handle/tede/12476 |
identifier_str_mv |
NAVES, L. M. Contribuição da neurotransmissão glutamatérgica na região rostroventrolateral do bulbo (RVLM) para as respostas cardiovasculares e autonômicas induzidas pelo fator de necrose tumoral alfa (TNF-α) no núcleo paraventricular do hipotálamo (PVN). 2022. 59 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Goiás, Goiânia, 2022. |
url |
http://repositorio.bc.ufg.br/tede/handle/tede/12476 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.program.fl_str_mv |
15 |
dc.relation.confidence.fl_str_mv |
500 500 500 500 |
dc.relation.department.fl_str_mv |
23 |
dc.relation.cnpq.fl_str_mv |
172 |
dc.relation.sponsorship.fl_str_mv |
0 |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.publisher.program.fl_str_mv |
Programa de Pós-graduação em Ciências Biológicas (ICB) |
dc.publisher.initials.fl_str_mv |
UFG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Instituto de Ciências Biológicas - ICB (RG) |
publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFG instname:Universidade Federal de Goiás (UFG) instacron:UFG |
instname_str |
Universidade Federal de Goiás (UFG) |
instacron_str |
UFG |
institution |
UFG |
reponame_str |
Repositório Institucional da UFG |
collection |
Repositório Institucional da UFG |
bitstream.url.fl_str_mv |
http://repositorio.bc.ufg.br/tede/bitstreams/594a5d3e-a525-4bee-b8ae-470376392d65/download http://repositorio.bc.ufg.br/tede/bitstreams/65e6fe48-ee3e-448c-8b20-ebbe031d5858/download http://repositorio.bc.ufg.br/tede/bitstreams/a95dc0e5-39e6-44a1-aae8-19d2fe7e1245/download |
bitstream.checksum.fl_str_mv |
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bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFG - Universidade Federal de Goiás (UFG) |
repository.mail.fl_str_mv |
tasesdissertacoes.bc@ufg.br |
_version_ |
1793965698990473216 |