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Envolvimento dos neuronios aferentes primarios sensiveis a capsaicina nas funções cardiacas de ratos

Orientador: Edson Antunes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-07-27T12:46:48Z (GMT). No. of bitstreams: 1
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Previous issue date: 2000 / Resumo: Os neuropeptídeos liberados dos neurônios sensoriais modulam as funções cardíacas. Recentemente, sugeriu-se a existência de uma interação funcional entre as fibras simpáticas, parassimpáticas e sensoriais em corações e vasos. O objetivo deste trabalho foi investigar os efeitos do tratamento neonatal com capsaicina sobre a potência do isoproterenol, carbacol, pilocarpina e/ou CGRP em átrio direito isolado de rato, bem como, o cronotropismo, inotropismo e fluxo coronariano em resposta aos agonistas a- e J3¬ adrenérgicos em coração isolado de rato. Ratos Wistar neonatos foram tratados com capsaicina (50 mg/Kg, subcutâneo) ou seu volume correspondente de veículo no segundo dia de vida. O coração e o átrio direito foram isolados 30, 60 e/ou 90 dias após tratamento. O tratamento com capsaicina determinou dessensibilização da resposta cronotrópica ao isoproterenol em átrios direitos de ratos de 30 dias, mas nenhuma alteração significativa foi observada nos animais com 60 ou 90 dias de idade. As respostas ao CGRP, carbacol e pilocarpina em átrios direitos não foram afetadas pelo tratamento neonatal com capsaicina em nenhum dos tempos estudados. A potência ao CGRP nos animais sacrificados aos 30 dias, para ambos os grupos, foi significativamente maior do que nos animais sacrificados aos 60 e 90 dias após o tratamento. O tratamento com capsaicina reduziu os conteúdos de CGRP 110 coração, em cerca de 74% em todos os tempos estudados; no entanto, a resposta funcional (cronotropismo positivo) à capsaicina exógena só foi significativamente atenuada aos 60 e 90 dias após tratamento. Em corações isolados, o fluxo coronariano basal foi reduzido aos 60 dias após tratamento, mas nenhuma alteração foi observada l1as respostas cronotrópicas e inotrópicas positivas ao isoproterenol e na vasoconstricção coronariana em resposta à fenileftina. Em resumo, a dessensibilização da resposta cronotrópica de átrios direitos nos animais com 30 dias de idade pode ser devido à intensa ativação do sistema simpato-adrenal acarretada pela capsaicina no período neonatal / Abstract: Sensory nerves in the heart are known to modulate cardiac functions by releasing neuropeptides. A functional cross-talk among sympathetic, parasympathetic and sensory nerves have been suggested in the heart and vascular beds. The aim of this work was to evaluate the effects of capsaicin treatment on the cardiac parameter changes, such as the potency of isoproterenol, carbachol, pilocarpine and/or CGRP in the rat isolated right atria, as well as, the changes of chronotropism, inotropism and/or coronary flow in response to a- (phenylephrine) and/or j3-(isoproterenol) adrenoceptor agonists using the Langendorff apparatus. Neonatal Wistar rats of both sexes were treated on the second day of life with capsaicin (50 mglkg, sc.) or the corresponding volume of vehicle solution. The heart and right atria were isolated at 30, 60 and/or 90 days after neonatal capsaicin¬treatment. The neonatal capsaicin-treatment caused a four-fold rightward shift at pECso leveI on the concentration-response curve (CRC) to isoproterenol at 30 days, whereas no changes were observed at 60 and 90 days. The CRC to CGRP, carbachol, and pilocarpine were not changed in all studied time. The potency of CGRP in isolated right atria in 30¬day-old rats was significantly higher than 60- and 90-day-old rats, as observed in both control and capsaicin groups. The increase of basal rate to addition of capsaicin on 90-day¬ old rats was markedly lower than 30- and 60-day-old animaIs in both studied groups. The CGRP receptor antagonist CGRP8-37 abolished the increased chronotropism to capsaicin in all studied groups. The neonatal capsaicin treatment reduced by aproximately 74% the CGRP content in the heart and the depletion percent was similar in all studied time. yv e found that neonatal capsaicin-treatment caused a significant reduction in basal coronary flow only at 60 days post-treatment. The positive chronotropic and inotropic responses to isoproterenol and the contractile response to phenilephrine were unaffected by the neonatal capsaicin-treatment at either 60 or 90 days. Our findings suggest that the desensitization.of chronotropic response mediated by j3-adrenoceptors observed at 3 O days after neonatal capsaicin-treatment is due to a massive activation of the sympato-adrenal system. It can not be attributed to sensory reinriervation since similar CGRP depletion was detected in all capsaicin-treated groups. No changes on the negative chronotropic responses to muscarinic agonists in isolated right atria were seen in neonatal capsaicin-treated rats indicating that sensory fibers do not influence parasympathe~ic fibers in rat cardiac tissue. The blockade of positive chronotropic responses to capsaicin by the CGRP8-37 indicate that capsaicin actions are fully mediated by CGRP. The highest potency for both CGRP and exogenous capsaicin, as well as, the basal rate in 30-day-old rats suggest that the density of CGRP¬containing fibers in young rats is greater than aged ones. The reduction of basal coronary flow at 60 days after capsaicin-treatment is a consequence of CGRP depletion. The restoration of coronary flow at 90 days post-capsaicin-treatment can be indicative of adaptive mechanisms to reverse this effect. The absence of changes on the cardiac parameters of isolated heart in response to adrenergic agents after neonatal capsaicin¬treatment at 60 and 90 days, exclude the existence of a cross-talk between sensory and sympathetic fibers at aged rats / Mestrado / Farmacologia / Mestre em Farmacologia

Identiferoai:union.ndltd.org:IBICT/oai:repositorio.unicamp.br:REPOSIP/308930
Date13 December 2000
CreatorsGasparetti, Alessandra Lia
ContributorsUNIVERSIDADE ESTADUAL DE CAMPINAS, Antunes, Edson, 1960-, Spadari-Brarfisch, Regina Celia, Oliveira, Ana Maria de
Publisher[s.n.], Universidade Estadual de Campinas. Faculdade de Ciências Médicas, Programa de Pós-Graduação em Ciências Médicas
Source SetsIBICT Brazilian ETDs
LanguagePortuguese
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis
Format90f. : il., application/pdf
Sourcereponame:Repositório Institucional da Unicamp, instname:Universidade Estadual de Campinas, instacron:UNICAMP
Rightsinfo:eu-repo/semantics/openAccess

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