Efeitos cardiorrespiratórios do β-citronelol : envolvimento de fibras aferentes vagais e ação direta em músculos liso e cardíaco

Detalhes bibliográficos
Ano de defesa: 2015
Autor(a) principal: Ribeiro Filho, Helder Veras
Orientador(a): Magalhães, Pedro Jorge Caldas
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/12852
Resumo: β-Citronellol is a monoterpene found in the essential oil of various aromatic plants used in folk medicine to treat hypertension such as Cymbopogon citratus. β-Citronellol possesses hypotensive and vasorelaxant properties, but the mechanism of such effects remains unclear. Therefore, the present study was undertaken to address this issue in normotensive rats. For in vivo experiments, male Wistar rats were subjected to catheterization of the left femoral artery and vein for mean arterial pressure monitoring and drug injection, respectively. Electrodes allowed heart rate recordings and some groups of rats were tracheostomized for respiratory rate analysis. For in vitro experiments, right and left atria, and mesenteric artery rings were suspended in organ baths at physiological conditions. In urethane-anesthetized rats, intravenous (i.v.) injections of β-citronellol (5 and 10 mg/kg) caused biphasic (phase 1 and phase 2) hypotension, bradycardia and apnea responses. Biphasic responses was observed also following i.v. injection of β-citronellol (5, 10 and 20 mg/kg) in unanesthetized rats. Phase 1 of this triad (onset time of 1-2 s) was abolished by bilateral vagotomy (BV), perineural treatment with capsaicin (PNT) or pretreatment with methylatropine (MA, i.v.), but remained unaltered by i.v. pretreatment with capsazepine, ondansetron, suramin or HC-030031. Phase 1 responses was absent when β-citronellol was injected into the left ventricle. The delayed phase 2 of bradycardia was also partially reduced by BV, PNT or MA while the apnea component of this phase 2 was only abolished by suramin. In atrial preparations, β-citronellol induced chronotropic and inotropic negative responses, an effect that was related to neither muscarinic and adrenergic receptor activation nor to altered calcium influx. In both endothelium-intact and denuded mesenteric artery rings, β-citronellol fully relaxed phenylephrine-induced contractions in a concentration-dependent manner and with equal potency. These findings reveal that the effects evoked by β-citronellol induced vago-vagal reflex due to stimulation of vagal pulmonary afferents, an effect that seems not involving TRPV1, TRPA1, 5-HT3, or P2X receptors. Phase 2 hypotensive and bradycardiac responses to β-citronellol appears resulting from a direct vasodilatory effect upon vascular smooth muscle and cardiac depressor action, respectively. Furthermore, P2X receptors seem to be involved in the mediation of phase 2 apneic response to this acyclic monoterpene.
id UFC-7_5afe723aa254ab350f72086fe94bbcd5
oai_identifier_str oai:repositorio.ufc.br:riufc/12852
network_acronym_str UFC-7
network_name_str Repositório Institucional da Universidade Federal do Ceará (UFC)
repository_id_str
spelling Ribeiro Filho, Helder VerasMagalhães, Pedro Jorge Caldas2015-06-17T13:40:24Z2015-06-17T13:40:24Z2015RIBEIRO FILHO, H. V. Efeitos cardiorrespiratórios do β-citronelol : envolvimento de fibras aferentes vagais e ação direta em músculos liso e cardíaco. 2015. 79 f. Dissertação (Mestrado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2015.http://www.repositorio.ufc.br/handle/riufc/12852β-Citronellol is a monoterpene found in the essential oil of various aromatic plants used in folk medicine to treat hypertension such as Cymbopogon citratus. β-Citronellol possesses hypotensive and vasorelaxant properties, but the mechanism of such effects remains unclear. Therefore, the present study was undertaken to address this issue in normotensive rats. For in vivo experiments, male Wistar rats were subjected to catheterization of the left femoral artery and vein for mean arterial pressure monitoring and drug injection, respectively. Electrodes allowed heart rate recordings and some groups of rats were tracheostomized for respiratory rate analysis. For in vitro experiments, right and left atria, and mesenteric artery rings were suspended in organ baths at physiological conditions. In urethane-anesthetized rats, intravenous (i.v.) injections of β-citronellol (5 and 10 mg/kg) caused biphasic (phase 1 and phase 2) hypotension, bradycardia and apnea responses. Biphasic responses was observed also following i.v. injection of β-citronellol (5, 10 and 20 mg/kg) in unanesthetized rats. Phase 1 of this triad (onset time of 1-2 s) was abolished by bilateral vagotomy (BV), perineural treatment with capsaicin (PNT) or pretreatment with methylatropine (MA, i.v.), but remained unaltered by i.v. pretreatment with capsazepine, ondansetron, suramin or HC-030031. Phase 1 responses was absent when β-citronellol was injected into the left ventricle. The delayed phase 2 of bradycardia was also partially reduced by BV, PNT or MA while the apnea component of this phase 2 was only abolished by suramin. In atrial preparations, β-citronellol induced chronotropic and inotropic negative responses, an effect that was related to neither muscarinic and adrenergic receptor activation nor to altered calcium influx. In both endothelium-intact and denuded mesenteric artery rings, β-citronellol fully relaxed phenylephrine-induced contractions in a concentration-dependent manner and with equal potency. These findings reveal that the effects evoked by β-citronellol induced vago-vagal reflex due to stimulation of vagal pulmonary afferents, an effect that seems not involving TRPV1, TRPA1, 5-HT3, or P2X receptors. Phase 2 hypotensive and bradycardiac responses to β-citronellol appears resulting from a direct vasodilatory effect upon vascular smooth muscle and cardiac depressor action, respectively. Furthermore, P2X receptors seem to be involved in the mediation of phase 2 apneic response to this acyclic monoterpene.β-Citronelol é um monoterpeno encontrado no óleo essencial de diversas plantas aromáticas utilizadas na medicina popular para tratar hipertensão, como a Cymbopogon citratus. O β-citronelol possui propriedades hipotensoras e vasorrelaxantes, porém seu mecanismo ainda não está claro. Portanto, o presente estudo foi realizado para abordar essa questão em ratos normotensos. Para os experimentos in vivo, ratos Wistar macho foram submetidos a cateterização da artéria e veia femoral esquerda para registro da pressão arterial média e para administração de substâncias, respectivamente. Eletrodos permitiram o registro da frequência cardíaca e certos grupos de animais foram traqueostomizados para análise da frequência respiratória. Para os experimentos in vitro, os átrios direito e esquerdo, e anéis de artéria mesentérica foram suspensos em cubas para órgãos isolados sob condições fisiológicas. Em ratos anestesiados com uretana, injeções intravenosas (i.v.) de β-citronelol (5 e 10 mg/kg) causaram hipotensão, bradicardia e apneia em duas fases (fase 1 e fase 2), assim como em animais acordados (5, 10 e 20 mg/kg). A fase 1 dessa tríade (1 – 2 s de latência), foi abolida pela vagotomia bilateral (BV), pelo tratamento perineural com capsaicina (TP) ou pelo pré-tratamento com metilatropina (MA, i.v.), assim como pela injeção do β-citronelol dentro do ventrículo esquerdo, mas manteve-se inalterada pelo pré-tratamento i.v. com capsazepina, ondansetrona, suramina ou HC-030031. A fase 2 tardia de bradicardia foi também reduzida pela BV, TP ou MA, enquanto que a apneia de fase 2 foi abolida apenas pela suramina. Em preparações atriais, o β-citronelol induziu efeito cronotrópico e inotrópico negativos, os quais não parecem estar envolvidos com receptores muscarínicos ou adrenérgicos, ou alterações no influxo de cálcio. Em anéis de artéria mesentérica, com e sem endotélio, o β-citronelol relaxou totalmente pré-contrações de fenilefrina com equiparável potência. Esses resultados revelam que a fase 1 de efeitos do β-citronelol origina-se através de um reflexo vago-vagal resultante da estimulação de aferências pulmonares vagais, que parecem não envolver receptores TRPV1, TRPA1, 5-HT3 ou P2X. A fase 2 de hipotensão e bradicardia parece resultar de uma ação de vasodilatação direta e de um efeito cardíaco depressor, respectivamente. Além disso, receptores P2X parecem estar envolvidos na mediação da resposta de fase 2 de apneia induzida por esse monoterpeno acíclico.HipotensãoBradicardiaApneiaEfeitos cardiorrespiratórios do β-citronelol : envolvimento de fibras aferentes vagais e ação direta em músculos liso e cardíacoCardiorespiratory effects of β-citronellol : involvement of vagal afferent fibers and direct actions on cardiac and smooth musclesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81786http://repositorio.ufc.br/bitstream/riufc/12852/2/license.txt8c4401d3d14722a7ca2d07c782a1aab3MD52ORIGINAL2015_dis_hvribeiro filho.pdf2015_dis_hvribeiro filho.pdfapplication/pdf2922834http://repositorio.ufc.br/bitstream/riufc/12852/1/2015_dis_hvribeiro%20filho.pdf90787770a1d124b3e506577d71616b1bMD51riufc/128522019-10-21 09:24:39.36oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2019-10-21T12:24:39Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Efeitos cardiorrespiratórios do β-citronelol : envolvimento de fibras aferentes vagais e ação direta em músculos liso e cardíaco
dc.title.en.pt_BR.fl_str_mv Cardiorespiratory effects of β-citronellol : involvement of vagal afferent fibers and direct actions on cardiac and smooth muscles
title Efeitos cardiorrespiratórios do β-citronelol : envolvimento de fibras aferentes vagais e ação direta em músculos liso e cardíaco
spellingShingle Efeitos cardiorrespiratórios do β-citronelol : envolvimento de fibras aferentes vagais e ação direta em músculos liso e cardíaco
Ribeiro Filho, Helder Veras
Hipotensão
Bradicardia
Apneia
title_short Efeitos cardiorrespiratórios do β-citronelol : envolvimento de fibras aferentes vagais e ação direta em músculos liso e cardíaco
title_full Efeitos cardiorrespiratórios do β-citronelol : envolvimento de fibras aferentes vagais e ação direta em músculos liso e cardíaco
title_fullStr Efeitos cardiorrespiratórios do β-citronelol : envolvimento de fibras aferentes vagais e ação direta em músculos liso e cardíaco
title_full_unstemmed Efeitos cardiorrespiratórios do β-citronelol : envolvimento de fibras aferentes vagais e ação direta em músculos liso e cardíaco
title_sort Efeitos cardiorrespiratórios do β-citronelol : envolvimento de fibras aferentes vagais e ação direta em músculos liso e cardíaco
author Ribeiro Filho, Helder Veras
author_facet Ribeiro Filho, Helder Veras
author_role author
dc.contributor.author.fl_str_mv Ribeiro Filho, Helder Veras
dc.contributor.advisor1.fl_str_mv Magalhães, Pedro Jorge Caldas
contributor_str_mv Magalhães, Pedro Jorge Caldas
dc.subject.por.fl_str_mv Hipotensão
Bradicardia
Apneia
topic Hipotensão
Bradicardia
Apneia
description β-Citronellol is a monoterpene found in the essential oil of various aromatic plants used in folk medicine to treat hypertension such as Cymbopogon citratus. β-Citronellol possesses hypotensive and vasorelaxant properties, but the mechanism of such effects remains unclear. Therefore, the present study was undertaken to address this issue in normotensive rats. For in vivo experiments, male Wistar rats were subjected to catheterization of the left femoral artery and vein for mean arterial pressure monitoring and drug injection, respectively. Electrodes allowed heart rate recordings and some groups of rats were tracheostomized for respiratory rate analysis. For in vitro experiments, right and left atria, and mesenteric artery rings were suspended in organ baths at physiological conditions. In urethane-anesthetized rats, intravenous (i.v.) injections of β-citronellol (5 and 10 mg/kg) caused biphasic (phase 1 and phase 2) hypotension, bradycardia and apnea responses. Biphasic responses was observed also following i.v. injection of β-citronellol (5, 10 and 20 mg/kg) in unanesthetized rats. Phase 1 of this triad (onset time of 1-2 s) was abolished by bilateral vagotomy (BV), perineural treatment with capsaicin (PNT) or pretreatment with methylatropine (MA, i.v.), but remained unaltered by i.v. pretreatment with capsazepine, ondansetron, suramin or HC-030031. Phase 1 responses was absent when β-citronellol was injected into the left ventricle. The delayed phase 2 of bradycardia was also partially reduced by BV, PNT or MA while the apnea component of this phase 2 was only abolished by suramin. In atrial preparations, β-citronellol induced chronotropic and inotropic negative responses, an effect that was related to neither muscarinic and adrenergic receptor activation nor to altered calcium influx. In both endothelium-intact and denuded mesenteric artery rings, β-citronellol fully relaxed phenylephrine-induced contractions in a concentration-dependent manner and with equal potency. These findings reveal that the effects evoked by β-citronellol induced vago-vagal reflex due to stimulation of vagal pulmonary afferents, an effect that seems not involving TRPV1, TRPA1, 5-HT3, or P2X receptors. Phase 2 hypotensive and bradycardiac responses to β-citronellol appears resulting from a direct vasodilatory effect upon vascular smooth muscle and cardiac depressor action, respectively. Furthermore, P2X receptors seem to be involved in the mediation of phase 2 apneic response to this acyclic monoterpene.
publishDate 2015
dc.date.accessioned.fl_str_mv 2015-06-17T13:40:24Z
dc.date.available.fl_str_mv 2015-06-17T13:40:24Z
dc.date.issued.fl_str_mv 2015
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv RIBEIRO FILHO, H. V. Efeitos cardiorrespiratórios do β-citronelol : envolvimento de fibras aferentes vagais e ação direta em músculos liso e cardíaco. 2015. 79 f. Dissertação (Mestrado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2015.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/12852
identifier_str_mv RIBEIRO FILHO, H. V. Efeitos cardiorrespiratórios do β-citronelol : envolvimento de fibras aferentes vagais e ação direta em músculos liso e cardíaco. 2015. 79 f. Dissertação (Mestrado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2015.
url http://www.repositorio.ufc.br/handle/riufc/12852
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:Repositório Institucional da Universidade Federal do Ceará (UFC)
instname:Universidade Federal do Ceará (UFC)
instacron:UFC
instname_str Universidade Federal do Ceará (UFC)
instacron_str UFC
institution UFC
reponame_str Repositório Institucional da Universidade Federal do Ceará (UFC)
collection Repositório Institucional da Universidade Federal do Ceará (UFC)
bitstream.url.fl_str_mv http://repositorio.ufc.br/bitstream/riufc/12852/2/license.txt
http://repositorio.ufc.br/bitstream/riufc/12852/1/2015_dis_hvribeiro%20filho.pdf
bitstream.checksum.fl_str_mv 8c4401d3d14722a7ca2d07c782a1aab3
90787770a1d124b3e506577d71616b1b
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
repository.name.fl_str_mv Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)
repository.mail.fl_str_mv bu@ufc.br || repositorio@ufc.br
_version_ 1847793296556949504