Relaxamento do corpo cavernoso de coelho induzido pela fração alcaloidal F3-5 de Aspidosperma ulei Markgr

Detalhes bibliográficos
Ano de defesa: 2007
Autor(a) principal: Goes Júnior, Francisco de Assis Mendes
Orientador(a): Silva, Lúcio Flávio Gonzaga
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/7320
Resumo: Erectile dysfunction is a worldwide public health issue and, in spite of advances brougth by the utilization of type-5 phosphodiesterase inhibitors, there is still much interest in new treatment alternatives, especially when derived from natural products. Some investigators observed the pro-erectile effects of an alkaloidal-rich fraction from Aspidosperma ulei Markgr., named F3-5. In this study, it was evaluated the degree of relaxation induced by F3-5 on rabbit corpus cavernosum, as well as possible Pharmacological mechanisms involved, in vitro. Several experimental assays were performed, utilizing the methods of cascade tissue superfusion and isolated tissue bath. Wíth strips ot corpus cavernosum pre-contracted with phenilephrine (5µM), dose-response curves of relaxation for F3-5 papaverine and DMSO were produced. were There were also assays fo, evaluation of the effects of L-NAME, 7-NI, 000, propranolol, atropine, sildenafil and F3-5 on the relaxations mediated by sodium litroprusside, acetylcholine, isoproterenol, sildenafil and F3-S. With depolarized preparations of corpus cavernosum, in a calcium-free, potassium-rich (60 mM) medium, the effects of F3-S and DMSO on the contractions induced by the progressive increase in Ca2+ concentration (1 - 300 mM) were observed. F3-5 was capable of inducing complete relaxation of rabbit corpus cavernosum with magnitude similar to that of papaverine for all doses tested, except 3 mg, when ít presented a significantly higher relaxation. Superfusions of L-NAME, 7-NI and ODQ did not significantly inhibit the relaxatíons provoked by F3-5, suggesting that it acts independently of the nitrergiê pathway. Propranolol and atropine also did not significantly interfere with relaxations mediated by F3-5 indicating that B-adrenergic or rnuscarinic receptors also might not be involved. F3-5 did not significantly amplify the relaxations promoted by sodium nitroprusside or acetylcholine, as opposed to sildenafil, suggesting that it does not act through inhibition of type-5 ohosphodiesterase. Finally, in cavernous tissue pre-incubated with F3-5, the minimum dose of Ca2+ necessary for muscular contraction was thirty times superior to that utilizedon the tissue without previous treatment, or treated with OMSO. This inhibition of the contractions of corpus cavernosum mediated by Ca2+ suggests, therefore, that F3-S can act through blockade of voltage-dependent calcium channels.
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spelling Goes Júnior, Francisco de Assis MendesSilva, Lúcio Flávio Gonzaga2014-02-19T16:38:19Z2014-02-19T16:38:19Z2007GOES JÚNIOR, Francisco de Assis Mendes. Relaxamento do corpo cavernoso de coelho induzido pela fração alcaloidal F3-5 de Aspidosperma ulei Markgr. 2007. 65 f. Dissertação (Mestrado em Cirurgia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2007.http://www.repositorio.ufc.br/handle/riufc/7320Erectile dysfunction is a worldwide public health issue and, in spite of advances brougth by the utilization of type-5 phosphodiesterase inhibitors, there is still much interest in new treatment alternatives, especially when derived from natural products. Some investigators observed the pro-erectile effects of an alkaloidal-rich fraction from Aspidosperma ulei Markgr., named F3-5. In this study, it was evaluated the degree of relaxation induced by F3-5 on rabbit corpus cavernosum, as well as possible Pharmacological mechanisms involved, in vitro. Several experimental assays were performed, utilizing the methods of cascade tissue superfusion and isolated tissue bath. Wíth strips ot corpus cavernosum pre-contracted with phenilephrine (5µM), dose-response curves of relaxation for F3-5 papaverine and DMSO were produced. were There were also assays fo, evaluation of the effects of L-NAME, 7-NI, 000, propranolol, atropine, sildenafil and F3-5 on the relaxations mediated by sodium litroprusside, acetylcholine, isoproterenol, sildenafil and F3-S. With depolarized preparations of corpus cavernosum, in a calcium-free, potassium-rich (60 mM) medium, the effects of F3-S and DMSO on the contractions induced by the progressive increase in Ca2+ concentration (1 - 300 mM) were observed. F3-5 was capable of inducing complete relaxation of rabbit corpus cavernosum with magnitude similar to that of papaverine for all doses tested, except 3 mg, when ít presented a significantly higher relaxation. Superfusions of L-NAME, 7-NI and ODQ did not significantly inhibit the relaxatíons provoked by F3-5, suggesting that it acts independently of the nitrergiê pathway. Propranolol and atropine also did not significantly interfere with relaxations mediated by F3-5 indicating that B-adrenergic or rnuscarinic receptors also might not be involved. F3-5 did not significantly amplify the relaxations promoted by sodium nitroprusside or acetylcholine, as opposed to sildenafil, suggesting that it does not act through inhibition of type-5 ohosphodiesterase. Finally, in cavernous tissue pre-incubated with F3-5, the minimum dose of Ca2+ necessary for muscular contraction was thirty times superior to that utilizedon the tissue without previous treatment, or treated with OMSO. This inhibition of the contractions of corpus cavernosum mediated by Ca2+ suggests, therefore, that F3-S can act through blockade of voltage-dependent calcium channels.A disfunção erétil é um problema mundial de saúde pública e, apesar dos avanços trazidos pela utilização dos inibidores da fosfodiesterase tipo-5, ainda há muito interesse em novas alternativas de tratamento, especialmente quando derivadas de produtos naturais. Alguns pesquisadores observaram os efeitos pró-eréteis de uma fração rica em alcalóides de Aspidosperma ulei Markgr., denominada F3-5. Neste estudo, foi avaliado o grau de relaxamento induzido por F3-5 no corpo cavernoso de coelho, bem como possíveis mecanismos farmacológicos envolvidos, in vitro. Foram realizados diversos ensaios experimentais, utilizando-se os métodos de superfusão de tecido em cascata e de banho isolado de tecido. Com tiras de corpo cavernoso pré-contraídas com fenilefrina (5 μM), foram produzidas curvas de dose-resposta de relaxamento para F3-5, papaverina e DMSO. Também foram realizados ensaios para avaliação dos efeitos de L-NAME, 7-NI, ODQ, propranolol, atropina, sildenafil e F3-5 sobre os relaxamentos mediados por nitroprussiato de sódio, acetilcolina, isoproterenol, sildenafil e F3-5. Com preparações de corpo cavernoso despolarizadas, em um meio livre de cálcio e rico em potássio (60 mM), os efeitos de F3-5 e DMSO sobre as contrações induzidas pelo aumento progressivo na concentração de Ca2+ (1 – 300 mM) foram observados. F3-5 foi capaz de induzir o relaxamento completo do corpo cavernoso de coelho, com magnitude similar à da papaverina para todas as doses testadas, exceto 3 mg, quando apresentou relaxamento significantemente maior. As superfusões de L-NAME, 7-NI e ODQ não inibiram significantemente os relaxamentos provocados por F3-5, sugerindo que este age independentemente da via nitrérgica. Propranolol e atropina também não interferiram significantemente com os relaxamentos mediados por F3-5, indicando que receptores β-adrenérgicos ou muscarínicos também não devem estar envolvidos. F3-5 não amplificou significantemente os relaxamentos promovidos por nitroprussiato de sódio ou acetilcolina, ao contrário de sildenafil, sugerindo que não age por inibição da fosfodiesterase tipo-5. Finalmente, em tecido cavernoso pré-incubado com F3-5, a dose mínima de Ca2+ necessária para contração muscular foi trinta vezes superior àquela utilizada em tecido sem tratamento prévio ou tratado com DMSO. Esta inibição das contrações de corpo cavernoso mediadas pelo Ca2+ sugere, portanto, que F3-5 pode atuar através do bloqueio de canais de cálcio voltagem-dependente.GMP CíclicoRelaxamento MuscularRelaxamento do corpo cavernoso de coelho induzido pela fração alcaloidal F3-5 de Aspidosperma ulei MarkgrRelaxation on of rabbit corpus cavernosum induced by the alkaloidal fraction F3-S from - Aspdidosperma ulei Markgrinfo: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/7320/2/license.txt8c4401d3d14722a7ca2d07c782a1aab3MD52ORIGINAL2007_dis_famgoesjpunior.pdf2007_dis_famgoesjpunior.pdfapplication/pdf1185630http://repositorio.ufc.br/bitstream/riufc/7320/1/2007_dis_famgoesjpunior.pdfbc50b6e04e8e3c6c6879faa44b04e3beMD51riufc/73202018-12-14 09:23:54.852oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2018-12-14T12:23:54Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Relaxamento do corpo cavernoso de coelho induzido pela fração alcaloidal F3-5 de Aspidosperma ulei Markgr
dc.title.en.pt_BR.fl_str_mv Relaxation on of rabbit corpus cavernosum induced by the alkaloidal fraction F3-S from - Aspdidosperma ulei Markgr
title Relaxamento do corpo cavernoso de coelho induzido pela fração alcaloidal F3-5 de Aspidosperma ulei Markgr
spellingShingle Relaxamento do corpo cavernoso de coelho induzido pela fração alcaloidal F3-5 de Aspidosperma ulei Markgr
Goes Júnior, Francisco de Assis Mendes
GMP Cíclico
Relaxamento Muscular
title_short Relaxamento do corpo cavernoso de coelho induzido pela fração alcaloidal F3-5 de Aspidosperma ulei Markgr
title_full Relaxamento do corpo cavernoso de coelho induzido pela fração alcaloidal F3-5 de Aspidosperma ulei Markgr
title_fullStr Relaxamento do corpo cavernoso de coelho induzido pela fração alcaloidal F3-5 de Aspidosperma ulei Markgr
title_full_unstemmed Relaxamento do corpo cavernoso de coelho induzido pela fração alcaloidal F3-5 de Aspidosperma ulei Markgr
title_sort Relaxamento do corpo cavernoso de coelho induzido pela fração alcaloidal F3-5 de Aspidosperma ulei Markgr
author Goes Júnior, Francisco de Assis Mendes
author_facet Goes Júnior, Francisco de Assis Mendes
author_role author
dc.contributor.author.fl_str_mv Goes Júnior, Francisco de Assis Mendes
dc.contributor.advisor1.fl_str_mv Silva, Lúcio Flávio Gonzaga
contributor_str_mv Silva, Lúcio Flávio Gonzaga
dc.subject.por.fl_str_mv GMP Cíclico
Relaxamento Muscular
topic GMP Cíclico
Relaxamento Muscular
description Erectile dysfunction is a worldwide public health issue and, in spite of advances brougth by the utilization of type-5 phosphodiesterase inhibitors, there is still much interest in new treatment alternatives, especially when derived from natural products. Some investigators observed the pro-erectile effects of an alkaloidal-rich fraction from Aspidosperma ulei Markgr., named F3-5. In this study, it was evaluated the degree of relaxation induced by F3-5 on rabbit corpus cavernosum, as well as possible Pharmacological mechanisms involved, in vitro. Several experimental assays were performed, utilizing the methods of cascade tissue superfusion and isolated tissue bath. Wíth strips ot corpus cavernosum pre-contracted with phenilephrine (5µM), dose-response curves of relaxation for F3-5 papaverine and DMSO were produced. were There were also assays fo, evaluation of the effects of L-NAME, 7-NI, 000, propranolol, atropine, sildenafil and F3-5 on the relaxations mediated by sodium litroprusside, acetylcholine, isoproterenol, sildenafil and F3-S. With depolarized preparations of corpus cavernosum, in a calcium-free, potassium-rich (60 mM) medium, the effects of F3-S and DMSO on the contractions induced by the progressive increase in Ca2+ concentration (1 - 300 mM) were observed. F3-5 was capable of inducing complete relaxation of rabbit corpus cavernosum with magnitude similar to that of papaverine for all doses tested, except 3 mg, when ít presented a significantly higher relaxation. Superfusions of L-NAME, 7-NI and ODQ did not significantly inhibit the relaxatíons provoked by F3-5, suggesting that it acts independently of the nitrergiê pathway. Propranolol and atropine also did not significantly interfere with relaxations mediated by F3-5 indicating that B-adrenergic or rnuscarinic receptors also might not be involved. F3-5 did not significantly amplify the relaxations promoted by sodium nitroprusside or acetylcholine, as opposed to sildenafil, suggesting that it does not act through inhibition of type-5 ohosphodiesterase. Finally, in cavernous tissue pre-incubated with F3-5, the minimum dose of Ca2+ necessary for muscular contraction was thirty times superior to that utilizedon the tissue without previous treatment, or treated with OMSO. This inhibition of the contractions of corpus cavernosum mediated by Ca2+ suggests, therefore, that F3-S can act through blockade of voltage-dependent calcium channels.
publishDate 2007
dc.date.issued.fl_str_mv 2007
dc.date.accessioned.fl_str_mv 2014-02-19T16:38:19Z
dc.date.available.fl_str_mv 2014-02-19T16:38:19Z
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dc.identifier.citation.fl_str_mv GOES JÚNIOR, Francisco de Assis Mendes. Relaxamento do corpo cavernoso de coelho induzido pela fração alcaloidal F3-5 de Aspidosperma ulei Markgr. 2007. 65 f. Dissertação (Mestrado em Cirurgia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2007.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/7320
identifier_str_mv GOES JÚNIOR, Francisco de Assis Mendes. Relaxamento do corpo cavernoso de coelho induzido pela fração alcaloidal F3-5 de Aspidosperma ulei Markgr. 2007. 65 f. Dissertação (Mestrado em Cirurgia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2007.
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