Avaliação dos efeitos de peptídeos isolados de veneno de serpentes no sistema cardiovascular de ratos
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFG |
Texto Completo: | http://repositorio.bc.ufg.br/tede/handle/tede/6233 |
Resumo: | The proline-riche-oligopeptides (PROs) were identified in the crude venom of snakes Bothrops jararaca (Bj), Bothrops cotiara (Bc) and Bothrops fonsecai (Bf). Previous studies have shown hypotensive/antihypertensive effects of the PROs in normotensive and hypertensive (SHR) rats. However, the direct effect of PROs in the aorta and heart isolated, as well as, the action mechanisms involved in these effects is unknown. In the presenty study, were evaluated the cardiovascular effect of six PROs, Bj-PRO-5a,-7a,-10c, Bc-PRO-10e, Bf-PRO-10d,-10f. The aortic rings, with (E+) or without (E-) endothelium, were preconstricted with phenylephine (Phe, 0.1 μmol/L), following increasing concentrations of PROs (0.1 nmol/L – 1 μmol/L) in presence or absence of a nonselective antagonist muscarinic receptors (Atropine, 3µmol/L), M1 muscarinic receptor antagonist (Pirenzepine, 1 µmol/L), synthase nitric oxide inhibitor (L-NAME, 1 µmol/L), adenylyl cyclase inhibitor (MDL 12.330A, 3 µmol/L), guanylyl cyclase inhibitor (ODQ, 3µmol/L) or argininosuccinate synthetase inhibitor (MDLA, 1 µmol/L). To evaluated the coronary and cardiac contractility effects of PROs, the hearts were perfused according Langendorff technique. The hearts were perfused for a basal period with Krebs Ringer solution containing the PROs (0.05 or 5 nmol/L) in presence or absence of L-NAME (10 nmol/L), ODQ (200 nmol/L) or MDL (1 µmol/L). The PROs utilized in this study induced endothelium-dependend vasorelaxation in aortic rings of Wistars and SHRs. Atropine and pirezenpine blocked the vasorelaxant effect of Bj-PRO-7a in isolated aorta from Wistar and SHR. L-NAME, ODQ or MDL inhibited the aortic vasorelaxation induced by Bj-PRO-7a and Bj-PRO-10c in both strains. MDLA inhibited the Bj-PRO-10c-induced vasorelaxation in aortic rings of SHR, but not in Wistar. Just the peptides Bj-PRO-7a and Bj-PRO-10c promoted a significant coronary vasodilatation in isolated heart from Wistar and SHR rats. The coronary vasodilatation induced by Bj-PRO-7a was inhibited in the presence of L-NAME in isolated heart from Wistar. Already in isolated heart from SHR this effect was abolished by L-NAME, ODQ or MDL. The Bc-PRO-10e and Bf-PRO-10f did not induce significant effects on cardiac contractility. However, the Bj-PRO-5a, -7a, -10c and Bf-PRO-10f promoted negative inotropic effect in the isolated hearts from Wistar and/or SHR. This effect in isolated hearts perfused by Bj-PRO-7a was inhibited in the presence of L-NAME in Wistars. Differently, the effect of Bj-PRO-10c was blocked by L-NAME, ODQ or MDL in both strains. Sumarizing, the PROs utilized in this study induced endothelium-dependend vasorelaxation. The data demonstrated participation of pathways NO/GCs/GMPc and AC/AMPc in the vasorelaxant effect of peptides Bj-PRO-7a and Bj-PRO-10c. In addition, the muscarinic receptors are involved in the vasorelaxant effects induced by peptide Bj-PRO-7a in aortic rings from Wistar and SHR rats. Moreover, the negative inotropic effect induced by Bj-PRO-7a and Bj-PRO-10c is linked with activation of NO in cardiomyocyte of normotensive and hypertensive rats. |
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Alves, Carlos Henriquehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4758015Z0Ianzer, Danielle Alveshttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4760882T6Castro, Carlos Henrique deIanzer, Danielle AlvesGhedini, Paulo Cesarhttps://wwws.cnpq.br/cvlattesweb/PKG_MENU.menu?f_cod=C3881249361BA6338532479C4CFC8033Alves, Pedro Henrique2016-09-19T13:13:55Z2016-03-22ALVES, P. H. Avaliação dos efeitos de peptídeos isolados de veneno de serpentes no sistema cardiovascular de ratos. 2016. 70 f. Dissertação (Mestrado em Ciências Fisiológicas) - Universidade Federal de Goiás, Goiânia, 2016.http://repositorio.bc.ufg.br/tede/handle/tede/6233ark:/38995/0013000006d2mThe proline-riche-oligopeptides (PROs) were identified in the crude venom of snakes Bothrops jararaca (Bj), Bothrops cotiara (Bc) and Bothrops fonsecai (Bf). Previous studies have shown hypotensive/antihypertensive effects of the PROs in normotensive and hypertensive (SHR) rats. However, the direct effect of PROs in the aorta and heart isolated, as well as, the action mechanisms involved in these effects is unknown. In the presenty study, were evaluated the cardiovascular effect of six PROs, Bj-PRO-5a,-7a,-10c, Bc-PRO-10e, Bf-PRO-10d,-10f. The aortic rings, with (E+) or without (E-) endothelium, were preconstricted with phenylephine (Phe, 0.1 μmol/L), following increasing concentrations of PROs (0.1 nmol/L – 1 μmol/L) in presence or absence of a nonselective antagonist muscarinic receptors (Atropine, 3µmol/L), M1 muscarinic receptor antagonist (Pirenzepine, 1 µmol/L), synthase nitric oxide inhibitor (L-NAME, 1 µmol/L), adenylyl cyclase inhibitor (MDL 12.330A, 3 µmol/L), guanylyl cyclase inhibitor (ODQ, 3µmol/L) or argininosuccinate synthetase inhibitor (MDLA, 1 µmol/L). To evaluated the coronary and cardiac contractility effects of PROs, the hearts were perfused according Langendorff technique. The hearts were perfused for a basal period with Krebs Ringer solution containing the PROs (0.05 or 5 nmol/L) in presence or absence of L-NAME (10 nmol/L), ODQ (200 nmol/L) or MDL (1 µmol/L). The PROs utilized in this study induced endothelium-dependend vasorelaxation in aortic rings of Wistars and SHRs. Atropine and pirezenpine blocked the vasorelaxant effect of Bj-PRO-7a in isolated aorta from Wistar and SHR. L-NAME, ODQ or MDL inhibited the aortic vasorelaxation induced by Bj-PRO-7a and Bj-PRO-10c in both strains. MDLA inhibited the Bj-PRO-10c-induced vasorelaxation in aortic rings of SHR, but not in Wistar. Just the peptides Bj-PRO-7a and Bj-PRO-10c promoted a significant coronary vasodilatation in isolated heart from Wistar and SHR rats. The coronary vasodilatation induced by Bj-PRO-7a was inhibited in the presence of L-NAME in isolated heart from Wistar. Already in isolated heart from SHR this effect was abolished by L-NAME, ODQ or MDL. The Bc-PRO-10e and Bf-PRO-10f did not induce significant effects on cardiac contractility. However, the Bj-PRO-5a, -7a, -10c and Bf-PRO-10f promoted negative inotropic effect in the isolated hearts from Wistar and/or SHR. This effect in isolated hearts perfused by Bj-PRO-7a was inhibited in the presence of L-NAME in Wistars. Differently, the effect of Bj-PRO-10c was blocked by L-NAME, ODQ or MDL in both strains. Sumarizing, the PROs utilized in this study induced endothelium-dependend vasorelaxation. The data demonstrated participation of pathways NO/GCs/GMPc and AC/AMPc in the vasorelaxant effect of peptides Bj-PRO-7a and Bj-PRO-10c. In addition, the muscarinic receptors are involved in the vasorelaxant effects induced by peptide Bj-PRO-7a in aortic rings from Wistar and SHR rats. Moreover, the negative inotropic effect induced by Bj-PRO-7a and Bj-PRO-10c is linked with activation of NO in cardiomyocyte of normotensive and hypertensive rats.Os oligopeptídeos ricos em prolina (PROs) foram identificados no veneno bruto das serpentes Bothrops jararaca (Bj), Bothrops cotiara (Bc) e Bothrops fonsecai (Bf). Estudos anteriores demonstram que os PROs promoveram efeitos hipotensor/anti-hipertensivo em ratos normotensos e espontaneamente hipertensos (SHR). No entanto, os efeitos diretos dos PROs em aorta e coração isolado, bem como, os mecanismos de ação envolvidos nestes efeitos são desconhecidos. No presente estudo, foram avaliados os efeitos cardiovasculares de seis PROs, Bj-PRO-5a, Bj-PRO-7a, Bj-PRO-10c, Bc-PRO-10e, Bf-PRO-10d e Bf-PRO-10f. Os anéis de aorta com (E+) e sem endotélio (E-) foram pré-constritos com fenilefrina (Phe, 0,1 µmol/L), seguido de concentrações cumulativas dos PROs (0,1 nmol/L – 1 µmol/L) na presença ou ausência de um antagonista não seletivo dos receptores muscarínicos (atropina, 3 µmol/L), antagonista do receptor muscarínico M1 (pirezenpina, 1 µmol/L), inibidor da óxido nítrico sintase (L-NAME, 3 µmol/L), inibidor da adenilato ciclase (MDL12,330a, 3 µmol/L), inibidor da guanilato ciclase (ODQ, 3 µmol/L) ou inibidor da argininosuccinato sintetase (MDLA, 1 µmol/L). Para avaliar os efeitos dos PROs na coronária e contratilidade cardíaca, os corações foram perfundidos de acordo com a técnica de Langendorff. Os corações foram perfundidos por um período basal com solução Krebs Ringer contendo os PROs (0,05 ou 5 nmol/L) na presença ou ausência de L-NAME (10 nmol/L, ODQ (200 nmol/L) ou MDL (1µmol/L). Todos os PROs utilizados neste estudo induziram vasorelaxamento dependente do endotélio em anéis de aorta de ratos Wistar e SHR. Atropina e pirenzepina bloquearam os efeito vasorelaxante do Bj-PRO-7a em aorta isolada de ratos Wistar e SHR. L-NAME, ODQ e MDL inibiram o vasorelaxamento induzido pelo Bj-PRO-7a e Bj-PRO-10c em ambas as linhagens. O MDLA inibiu o vasorelaxamento induzido pelo Bj-PRO-10c somente em anéis de aorta de SHRs. Somente os peptídeos Bj-PRO-7a e Bj-PRO-10c promoveram uma vasodilatação coronariana em corações isolados de ratos Wistar e SHR. A vasodilatação coronariana induzida pelo Bj-PRO-7a foi inibida na presença de L-NAME em corações de ratos Wistar. Já em corações isolados de SHRs este efeito abolido por com L-NAME, ODQ ou MDL. O Bc-PRO-10e e Bf-PRO-10f não induziram efeitos significantes na contratilidade cardíaca. No entanto, o Bj-PRO-5a, Bj-PRO-7a, Bj-PRO-10c e Bf-PRO-10f promoveram efeito inotrópico negativo em corações isolados de ratos Wistar e/ou SHRs. Este efeito desencadeado pelo Bj-PRO-7a foi inibido na presença de L-NAME em corações isolados de Wistar. Diferentemente, o efeito do Bj-PRO-10c foi bloqueado pelo L-NAME, ODQ ou MDL em ambas as linhagens. Sumarizando, os PROs utilizados neste estudo induziram vasorelaxamento dependente do endotélio. Os dados demonstram a participação das vias NO/GC/GMPc e AC/AMPc nos efeitos vasorelaxantes promovidos pelos peptídeos Bj-PRO-7a e Bj-PRO-10c. Além disso, os receptores muscarínicos estão envolvidos nos efeitos vasorelaxantes do peptídeo Bj-PRO-7a em anéis de ratos Wistar e SHRs. O efeito inotrópico negativo induzidos pelo Bj-PRO-7a e Bj-PRO-10c está relacionado com a ativação do NO em cardiomiócitos de ratos normotensos e hipertensos.Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2016-09-19T12:25:23Z No. of bitstreams: 2 Dissertação - Pedro Henrique Alves - 2016.pdf: 2763667 bytes, checksum: ed46b206ebbbad30bdfc2a13fa22abab (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-09-19T13:13:54Z (GMT) No. of bitstreams: 2 Dissertação - Pedro Henrique Alves - 2016.pdf: 2763667 bytes, checksum: ed46b206ebbbad30bdfc2a13fa22abab (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2016-09-19T13:13:55Z (GMT). No. of bitstreams: 2 Dissertação - Pedro Henrique Alves - 2016.pdf: 2763667 bytes, checksum: ed46b206ebbbad30bdfc2a13fa22abab (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-03-22Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESFundação de Amparo à Pesquisa do Estado de Goiás - FAPEGapplication/pdfporUniversidade Federal de GoiásPrograma de Pós-graduação em Ciências Fisiológicas - Multicêntrico (ICB)UFGBrasilInstituto de Ciências Biológicas - ICB (RG)http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessSistema cardiovascularPeptídeos isolados de venenos de serpentesCardiovascular systemPeptides isolated from snakes venomsCIENCIAS BIOLOGICAS::FISIOLOGIAAvaliação dos efeitos de peptídeos isolados de veneno de serpentes no sistema cardiovascular de ratosEvaluation of the effects of peptides isolated from snakes venoms in cardiovascular system of ratsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis1337318928839825463600600600600600-387277211782737340477377082474190182232075167498588264571-961409807440757778reponame:Repositório Institucional da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGORIGINALDissertação - Pedro Henrique Alves - 2016.pdfDissertação - Pedro Henrique Alves - 2016.pdfapplication/pdf2763667http://repositorio.bc.ufg.br/tede/bitstreams/1aaf07cd-baff-40a8-8f4e-4166a17231ce/downloaded46b206ebbbad30bdfc2a13fa22ababMD55LICENSElicense.txtlicense.txttext/plain; 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dc.title.por.fl_str_mv |
Avaliação dos efeitos de peptídeos isolados de veneno de serpentes no sistema cardiovascular de ratos |
dc.title.alternative.eng.fl_str_mv |
Evaluation of the effects of peptides isolated from snakes venoms in cardiovascular system of rats |
title |
Avaliação dos efeitos de peptídeos isolados de veneno de serpentes no sistema cardiovascular de ratos |
spellingShingle |
Avaliação dos efeitos de peptídeos isolados de veneno de serpentes no sistema cardiovascular de ratos Alves, Pedro Henrique Sistema cardiovascular Peptídeos isolados de venenos de serpentes Cardiovascular system Peptides isolated from snakes venoms CIENCIAS BIOLOGICAS::FISIOLOGIA |
title_short |
Avaliação dos efeitos de peptídeos isolados de veneno de serpentes no sistema cardiovascular de ratos |
title_full |
Avaliação dos efeitos de peptídeos isolados de veneno de serpentes no sistema cardiovascular de ratos |
title_fullStr |
Avaliação dos efeitos de peptídeos isolados de veneno de serpentes no sistema cardiovascular de ratos |
title_full_unstemmed |
Avaliação dos efeitos de peptídeos isolados de veneno de serpentes no sistema cardiovascular de ratos |
title_sort |
Avaliação dos efeitos de peptídeos isolados de veneno de serpentes no sistema cardiovascular de ratos |
author |
Alves, Pedro Henrique |
author_facet |
Alves, Pedro Henrique |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Alves, Carlos Henrique |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4758015Z0 |
dc.contributor.advisor-co1.fl_str_mv |
Ianzer, Danielle Alves |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4760882T6 |
dc.contributor.referee1.fl_str_mv |
Castro, Carlos Henrique de |
dc.contributor.referee2.fl_str_mv |
Ianzer, Danielle Alves |
dc.contributor.referee3.fl_str_mv |
Ghedini, Paulo Cesar |
dc.contributor.authorLattes.fl_str_mv |
https://wwws.cnpq.br/cvlattesweb/PKG_MENU.menu?f_cod=C3881249361BA6338532479C4CFC8033 |
dc.contributor.author.fl_str_mv |
Alves, Pedro Henrique |
contributor_str_mv |
Alves, Carlos Henrique Ianzer, Danielle Alves Castro, Carlos Henrique de Ianzer, Danielle Alves Ghedini, Paulo Cesar |
dc.subject.por.fl_str_mv |
Sistema cardiovascular Peptídeos isolados de venenos de serpentes |
topic |
Sistema cardiovascular Peptídeos isolados de venenos de serpentes Cardiovascular system Peptides isolated from snakes venoms CIENCIAS BIOLOGICAS::FISIOLOGIA |
dc.subject.eng.fl_str_mv |
Cardiovascular system Peptides isolated from snakes venoms |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::FISIOLOGIA |
description |
The proline-riche-oligopeptides (PROs) were identified in the crude venom of snakes Bothrops jararaca (Bj), Bothrops cotiara (Bc) and Bothrops fonsecai (Bf). Previous studies have shown hypotensive/antihypertensive effects of the PROs in normotensive and hypertensive (SHR) rats. However, the direct effect of PROs in the aorta and heart isolated, as well as, the action mechanisms involved in these effects is unknown. In the presenty study, were evaluated the cardiovascular effect of six PROs, Bj-PRO-5a,-7a,-10c, Bc-PRO-10e, Bf-PRO-10d,-10f. The aortic rings, with (E+) or without (E-) endothelium, were preconstricted with phenylephine (Phe, 0.1 μmol/L), following increasing concentrations of PROs (0.1 nmol/L – 1 μmol/L) in presence or absence of a nonselective antagonist muscarinic receptors (Atropine, 3µmol/L), M1 muscarinic receptor antagonist (Pirenzepine, 1 µmol/L), synthase nitric oxide inhibitor (L-NAME, 1 µmol/L), adenylyl cyclase inhibitor (MDL 12.330A, 3 µmol/L), guanylyl cyclase inhibitor (ODQ, 3µmol/L) or argininosuccinate synthetase inhibitor (MDLA, 1 µmol/L). To evaluated the coronary and cardiac contractility effects of PROs, the hearts were perfused according Langendorff technique. The hearts were perfused for a basal period with Krebs Ringer solution containing the PROs (0.05 or 5 nmol/L) in presence or absence of L-NAME (10 nmol/L), ODQ (200 nmol/L) or MDL (1 µmol/L). The PROs utilized in this study induced endothelium-dependend vasorelaxation in aortic rings of Wistars and SHRs. Atropine and pirezenpine blocked the vasorelaxant effect of Bj-PRO-7a in isolated aorta from Wistar and SHR. L-NAME, ODQ or MDL inhibited the aortic vasorelaxation induced by Bj-PRO-7a and Bj-PRO-10c in both strains. MDLA inhibited the Bj-PRO-10c-induced vasorelaxation in aortic rings of SHR, but not in Wistar. Just the peptides Bj-PRO-7a and Bj-PRO-10c promoted a significant coronary vasodilatation in isolated heart from Wistar and SHR rats. The coronary vasodilatation induced by Bj-PRO-7a was inhibited in the presence of L-NAME in isolated heart from Wistar. Already in isolated heart from SHR this effect was abolished by L-NAME, ODQ or MDL. The Bc-PRO-10e and Bf-PRO-10f did not induce significant effects on cardiac contractility. However, the Bj-PRO-5a, -7a, -10c and Bf-PRO-10f promoted negative inotropic effect in the isolated hearts from Wistar and/or SHR. This effect in isolated hearts perfused by Bj-PRO-7a was inhibited in the presence of L-NAME in Wistars. Differently, the effect of Bj-PRO-10c was blocked by L-NAME, ODQ or MDL in both strains. Sumarizing, the PROs utilized in this study induced endothelium-dependend vasorelaxation. The data demonstrated participation of pathways NO/GCs/GMPc and AC/AMPc in the vasorelaxant effect of peptides Bj-PRO-7a and Bj-PRO-10c. In addition, the muscarinic receptors are involved in the vasorelaxant effects induced by peptide Bj-PRO-7a in aortic rings from Wistar and SHR rats. Moreover, the negative inotropic effect induced by Bj-PRO-7a and Bj-PRO-10c is linked with activation of NO in cardiomyocyte of normotensive and hypertensive rats. |
publishDate |
2016 |
dc.date.accessioned.fl_str_mv |
2016-09-19T13:13:55Z |
dc.date.issued.fl_str_mv |
2016-03-22 |
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 |
ALVES, P. H. Avaliação dos efeitos de peptídeos isolados de veneno de serpentes no sistema cardiovascular de ratos. 2016. 70 f. Dissertação (Mestrado em Ciências Fisiológicas) - Universidade Federal de Goiás, Goiânia, 2016. |
dc.identifier.uri.fl_str_mv |
http://repositorio.bc.ufg.br/tede/handle/tede/6233 |
dc.identifier.dark.fl_str_mv |
ark:/38995/0013000006d2m |
identifier_str_mv |
ALVES, P. H. Avaliação dos efeitos de peptídeos isolados de veneno de serpentes no sistema cardiovascular de ratos. 2016. 70 f. Dissertação (Mestrado em Ciências Fisiológicas) - Universidade Federal de Goiás, Goiânia, 2016. ark:/38995/0013000006d2m |
url |
http://repositorio.bc.ufg.br/tede/handle/tede/6233 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.program.fl_str_mv |
1337318928839825463 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 600 |
dc.relation.department.fl_str_mv |
-3872772117827373404 |
dc.relation.cnpq.fl_str_mv |
7737708247419018223 |
dc.relation.sponsorship.fl_str_mv |
2075167498588264571 -961409807440757778 |
dc.rights.driver.fl_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.publisher.program.fl_str_mv |
Programa de Pós-graduação em Ciências Fisiológicas - Multicêntrico (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 |
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Repositório Institucional da UFG - Universidade Federal de Goiás (UFG) |
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tasesdissertacoes.bc@ufg.br |
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1811721415821361152 |