Participação dos receptores NK-1 no locus coeruleus na resposta cardiorrespiratória e termorreguladora à hipercapnia

Detalhes bibliográficos
Autor(a) principal: Carvalho, Débora de
Data de Publicação: 2009
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFSCAR
Texto Completo: https://repositorio.ufscar.br/handle/ufscar/1309
Resumo: The locus coeruleus (LC) has been suggested as a CO2 chemoreceptor site in mammals. Substance P (SP) has been used as a marker of respiratory neurons and it plays an important role in compensatory responses to hypercapnia in several sites of the central nervous system. Neurokinin-1 (NK-1) receptor immunoreactive (NK1Rir) neurons and processes are widely distributed within the LC. Thus, the present study assessed the role of NK-1 receptors in the LC in the cardiorespiratory and thermal responses to hypercapnia. To this end, substance P-saporin conjugate (SPSAP; 2μM) was injected in the LC to kill NK1R-ir neurons, or IgG-SAP as a control in male Wistar rats. The animals that the drug reached the fourth ventricle (4ºV) were considered as a 4ºV group. Pulmonary ventilation (VE, body plethysmograph), mean arterial pressure (MAP), heart rate (HR) and body core temperature were measured followed by 60 min of hypercapnic exposure (7% CO2). To verify the correct placement and effectiveness of the chemical lesions, immunohistochemistry for NK1R was performed. In addition, tyrosine hydroxylase (TH) immunoreactivity was performed to verify if noradrenergic neurons were eliminated. Fluoro-Jade technique was used to evaluate neuronal degeneration. A reduced NK1R (72% of reduction) and TH immunoreactivity (66% of reduction) was observed seven days after the injections of SP-SAP in the LC and an intense Fluoro-Jade staining, showing the effectiveness of the lesion. Focal lesions of NK1R-ir did not affect basal ventilation in the SP-SAP in LC and SP-SAP in 4ºV groups. Hypercapnia caused an increase in pulmonary ventilation in all groups, which was a result of increases in respiratory frequency (fR) and tidal volume (VT), SP-SAP treatment in the LC and in the fourth ventricle attenuated the hypercapnic ventilatory response (30% and 20%, respectivally), due to a reduction in the VT. SP-SAP in the LC and SP SAP in the 4ºV 11 lesion did not affect MAP, but caused an increase in HR in both groups. The results suggest that NK1R-ir neurons in the LC modulate hypercapnic ventilatory response but play no role in breathing control under resting conditions. Additionally, NK1R-ir neurons seem to play no role in body temperature and MAP regulation in resting conditions and during hypercapnia, but modulate HR during CO2 exposure. This modulation may be due to a change in the noradrenaline release.
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spelling Carvalho, Débora deBatalhão, Luciane Helena Gargaglionihttp://lattes.cnpq.br/5850453468994497http://lattes.cnpq.br/86130797235940912016-06-02T19:22:51Z2009-08-112016-06-02T19:22:51Z2009-05-29CARVALHO, Débora de. Participação dos receptores NK-1 no locus coeruleus na resposta cardiorrespiratória e termorreguladora à hipercapnia. 2009. 76 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de São Carlos, São Carlos, 2009.https://repositorio.ufscar.br/handle/ufscar/1309The locus coeruleus (LC) has been suggested as a CO2 chemoreceptor site in mammals. Substance P (SP) has been used as a marker of respiratory neurons and it plays an important role in compensatory responses to hypercapnia in several sites of the central nervous system. Neurokinin-1 (NK-1) receptor immunoreactive (NK1Rir) neurons and processes are widely distributed within the LC. Thus, the present study assessed the role of NK-1 receptors in the LC in the cardiorespiratory and thermal responses to hypercapnia. To this end, substance P-saporin conjugate (SPSAP; 2μM) was injected in the LC to kill NK1R-ir neurons, or IgG-SAP as a control in male Wistar rats. The animals that the drug reached the fourth ventricle (4ºV) were considered as a 4ºV group. Pulmonary ventilation (VE, body plethysmograph), mean arterial pressure (MAP), heart rate (HR) and body core temperature were measured followed by 60 min of hypercapnic exposure (7% CO2). To verify the correct placement and effectiveness of the chemical lesions, immunohistochemistry for NK1R was performed. In addition, tyrosine hydroxylase (TH) immunoreactivity was performed to verify if noradrenergic neurons were eliminated. Fluoro-Jade technique was used to evaluate neuronal degeneration. A reduced NK1R (72% of reduction) and TH immunoreactivity (66% of reduction) was observed seven days after the injections of SP-SAP in the LC and an intense Fluoro-Jade staining, showing the effectiveness of the lesion. Focal lesions of NK1R-ir did not affect basal ventilation in the SP-SAP in LC and SP-SAP in 4ºV groups. Hypercapnia caused an increase in pulmonary ventilation in all groups, which was a result of increases in respiratory frequency (fR) and tidal volume (VT), SP-SAP treatment in the LC and in the fourth ventricle attenuated the hypercapnic ventilatory response (30% and 20%, respectivally), due to a reduction in the VT. SP-SAP in the LC and SP SAP in the 4ºV 11 lesion did not affect MAP, but caused an increase in HR in both groups. The results suggest that NK1R-ir neurons in the LC modulate hypercapnic ventilatory response but play no role in breathing control under resting conditions. Additionally, NK1R-ir neurons seem to play no role in body temperature and MAP regulation in resting conditions and during hypercapnia, but modulate HR during CO2 exposure. This modulation may be due to a change in the noradrenaline release.O locus coeruleus (LC) é considerado uma região quimiorreceptora a CO2/pH em mamíferos. A substância P (SP) tem sido usada como marcador de neurônios respiratórios, pois possui importante função nas respostas compensatórias a hipercapnia em muitas áreas do sistema nervoso central. Neurônios e processos imunorreativos a receptores neurocinina 1 (NK-1) estão amplamente distribuídos dentro do LC. Portanto, o presente estudo teve por objetivo avaliar a participação de receptores NK-1 no LC nas respostas cardiorrespiratórias e termorreguladoras à hipercapnia. Para este fim, foi injetado o conjugado SP-Saporina (SP-SAP; 2μM) no LC de ratos Wistar para lesar neurônios que expressam esses receptores, ou IgGSAP como controle. Os animais em que as injeções atingiram o quarto ventrículo (4ºV) foram considerados como grupo 4ºV. A ventilação pulmonar (VE, pletismografia de corpo inteiro), pressão arterial média (PAM), freqüência cardíaca (FC) e temperatura corporal (Tc) foram medidas por 60 min de exposição à hipercapnia (7% CO2). Para verificar a correta localização e efetividade da lesão química realizou-se a imunohistoquímica para receptores NK-1. Além disso, imunohistoquímica para tirosina hidroxilase (TH) foi realizada para averigüar se neurônios noradrenérgicos foram lesados. A técnica de Fluoro-Jade foi também utilizada para avaliar a neurodegeneração. Observou-se a redução da imunorreatividade para receptores NK-1 (72% de lesão dos neurônios) e redução da imunorreatividade para neurônios noradrenérgicos (66% dos neurônios noradrenérgicos) sete dias após injeções de SP-SAP no LC e intensa marcação na técnica de Fluoro-Jade mostrando a efetividade da lesão. Lesões seletivas de neurônios que expressam receptores NK-1 no LC não afetaram a ventilação basal, o mesmo foi observado com os animais em que a injeção atingiu o 4ºV. A hipercapnia causou aumento da ventilação pulmonar 9 em todos os grupos decorrente do aumento da freqüência respiratória (fR) e volume corrente (VC). Entretanto, o tratamento com SP-SAP no LC e no 4ºV promoveu atenuação da resposta ventilatória (30% e 20%, respectivamente), devido à diminuição do VC. A lesão com SP-SAP no LC e no 4ºV não afetou a PAM, entretanto promoveu aumento na FC em ambos grupos. Os resultados sugerem que os neurônios que expressam receptores NK-1 no LC modulam a resposta ventilatória à hipercapnia, porém não possuem papel tônico na ventilação em condições basais. Além disso, esses neurônios não participam da regulação da temperatura e da PAM em normocapnia e hipercapnia, mas modulam FC durante exposição ao CO2. Essa modulação pode ser devida a alteração na liberação de noradrenalina.Universidade Federal de Minas Geraisapplication/pdfporUniversidade Federal de São CarlosPrograma Interinstitucional de Pós-Graduação em Ciências Fisiológicas - PIPGCFUFSCarBRRespiraçãoQuimiorrecepçãoLocus coeruleusSubstância PCO2A6QuimiossensibilidadeSubstance PChemosensitivityBreathingCIENCIAS BIOLOGICAS::FISIOLOGIAParticipação dos receptores NK-1 no locus coeruleus na resposta cardiorrespiratória e termorreguladora à hipercapniainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINAL2475.pdfapplication/pdf1572607https://{{ getenv "DSPACE_HOST" "repositorio.ufscar.br" }}/bitstream/ufscar/1309/1/2475.pdf64043b30c1df210d393c4540c2d88933MD51THUMBNAIL2475.pdf.jpg2475.pdf.jpgIM Thumbnailimage/jpeg9488https://{{ getenv "DSPACE_HOST" "repositorio.ufscar.br" }}/bitstream/ufscar/1309/2/2475.pdf.jpgc42c1178f865cad20190cc650115c736MD52ufscar/13092019-09-11 02:00:13.87oai:repositorio.ufscar.br:ufscar/1309Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222019-09-11T02:00:13Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false
dc.title.por.fl_str_mv Participação dos receptores NK-1 no locus coeruleus na resposta cardiorrespiratória e termorreguladora à hipercapnia
title Participação dos receptores NK-1 no locus coeruleus na resposta cardiorrespiratória e termorreguladora à hipercapnia
spellingShingle Participação dos receptores NK-1 no locus coeruleus na resposta cardiorrespiratória e termorreguladora à hipercapnia
Carvalho, Débora de
Respiração
Quimiorrecepção
Locus coeruleus
Substância P
CO2
A6
Quimiossensibilidade
Substance P
Chemosensitivity
Breathing
CIENCIAS BIOLOGICAS::FISIOLOGIA
title_short Participação dos receptores NK-1 no locus coeruleus na resposta cardiorrespiratória e termorreguladora à hipercapnia
title_full Participação dos receptores NK-1 no locus coeruleus na resposta cardiorrespiratória e termorreguladora à hipercapnia
title_fullStr Participação dos receptores NK-1 no locus coeruleus na resposta cardiorrespiratória e termorreguladora à hipercapnia
title_full_unstemmed Participação dos receptores NK-1 no locus coeruleus na resposta cardiorrespiratória e termorreguladora à hipercapnia
title_sort Participação dos receptores NK-1 no locus coeruleus na resposta cardiorrespiratória e termorreguladora à hipercapnia
author Carvalho, Débora de
author_facet Carvalho, Débora de
author_role author
dc.contributor.authorlattes.por.fl_str_mv http://lattes.cnpq.br/8613079723594091
dc.contributor.author.fl_str_mv Carvalho, Débora de
dc.contributor.advisor1.fl_str_mv Batalhão, Luciane Helena Gargaglioni
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/5850453468994497
contributor_str_mv Batalhão, Luciane Helena Gargaglioni
dc.subject.por.fl_str_mv Respiração
Quimiorrecepção
Locus coeruleus
Substância P
CO2
A6
Quimiossensibilidade
topic Respiração
Quimiorrecepção
Locus coeruleus
Substância P
CO2
A6
Quimiossensibilidade
Substance P
Chemosensitivity
Breathing
CIENCIAS BIOLOGICAS::FISIOLOGIA
dc.subject.eng.fl_str_mv Substance P
Chemosensitivity
Breathing
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::FISIOLOGIA
description The locus coeruleus (LC) has been suggested as a CO2 chemoreceptor site in mammals. Substance P (SP) has been used as a marker of respiratory neurons and it plays an important role in compensatory responses to hypercapnia in several sites of the central nervous system. Neurokinin-1 (NK-1) receptor immunoreactive (NK1Rir) neurons and processes are widely distributed within the LC. Thus, the present study assessed the role of NK-1 receptors in the LC in the cardiorespiratory and thermal responses to hypercapnia. To this end, substance P-saporin conjugate (SPSAP; 2μM) was injected in the LC to kill NK1R-ir neurons, or IgG-SAP as a control in male Wistar rats. The animals that the drug reached the fourth ventricle (4ºV) were considered as a 4ºV group. Pulmonary ventilation (VE, body plethysmograph), mean arterial pressure (MAP), heart rate (HR) and body core temperature were measured followed by 60 min of hypercapnic exposure (7% CO2). To verify the correct placement and effectiveness of the chemical lesions, immunohistochemistry for NK1R was performed. In addition, tyrosine hydroxylase (TH) immunoreactivity was performed to verify if noradrenergic neurons were eliminated. Fluoro-Jade technique was used to evaluate neuronal degeneration. A reduced NK1R (72% of reduction) and TH immunoreactivity (66% of reduction) was observed seven days after the injections of SP-SAP in the LC and an intense Fluoro-Jade staining, showing the effectiveness of the lesion. Focal lesions of NK1R-ir did not affect basal ventilation in the SP-SAP in LC and SP-SAP in 4ºV groups. Hypercapnia caused an increase in pulmonary ventilation in all groups, which was a result of increases in respiratory frequency (fR) and tidal volume (VT), SP-SAP treatment in the LC and in the fourth ventricle attenuated the hypercapnic ventilatory response (30% and 20%, respectivally), due to a reduction in the VT. SP-SAP in the LC and SP SAP in the 4ºV 11 lesion did not affect MAP, but caused an increase in HR in both groups. The results suggest that NK1R-ir neurons in the LC modulate hypercapnic ventilatory response but play no role in breathing control under resting conditions. Additionally, NK1R-ir neurons seem to play no role in body temperature and MAP regulation in resting conditions and during hypercapnia, but modulate HR during CO2 exposure. This modulation may be due to a change in the noradrenaline release.
publishDate 2009
dc.date.available.fl_str_mv 2009-08-11
2016-06-02T19:22:51Z
dc.date.issued.fl_str_mv 2009-05-29
dc.date.accessioned.fl_str_mv 2016-06-02T19:22:51Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.citation.fl_str_mv CARVALHO, Débora de. Participação dos receptores NK-1 no locus coeruleus na resposta cardiorrespiratória e termorreguladora à hipercapnia. 2009. 76 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de São Carlos, São Carlos, 2009.
dc.identifier.uri.fl_str_mv https://repositorio.ufscar.br/handle/ufscar/1309
identifier_str_mv CARVALHO, Débora de. Participação dos receptores NK-1 no locus coeruleus na resposta cardiorrespiratória e termorreguladora à hipercapnia. 2009. 76 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de São Carlos, São Carlos, 2009.
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