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Publico-121g.pdf: 1321792 bytes, checksum: 79c868582d382c14204c0f2a71cf7fd1 (MD5) / O NTS é o sítio primário das terminações das aferências dos reflexos cardiovasculares no sistema nervoso central (SNC). A presença da acetilcolina (ACh) no NTS e sua participação na transmissão ou modulação central das funções neurovegetativas foi sugerida desde a década de 80 (Kobayashi et al., 1978; Simon et al., 1981; Criscione et al., 1983; Helke et al., 1983). Contudo, a maioria dos estudos da literatura foram realizados in vitro e não há evidências de estudos da transmissão colinérgica in vivo em animais não anestesiados. Estudos prévios de nosso laboratório mostraram que a microinjeção de ACh no NTS de ratos não anestesiados causa hipotensão e bradicardia dose-dependentes e estas respostas parecem ser mediadas ou moduladas em parte pela liberação de óxido nítrico derivado da isoforma neuronal da enzima óxido nítrico sintase (NOS). A queda de pressão arterial causada pela ACh não foi abolida após o bloqueio parassimpático com metilatropina, indicando que a ativação do sistema colinérgico no NTS causa redução significante do componente simpático. A fim de discriminar as respostas de pressão arterial média (PAM) e frequência cardíaca (FC) causadas pela estimulação dos receptores colinérgicos nicotínicos e muscarínicos no NTS, realizamos as curvas dose-resposta para os agonistas seletivos nicotina (NIC) e pilocarpina (PIL) microinjetados no NTS de ratos não anestesiados. Além disso, investigamos também os efeitos do bloqueio central da NOS neuronal (TRIM) sobre estas respostas. Ratos Wistar foram preparados de acordo com a técnina de implante crônico de cânulas guia em direção ao NTS e da metodologia para microinjeção de drogas em animais não anestesiados e registro de pressão arterial in vivo. A microinjeção unilateral do agonista colinérgico de receptor nicotínico (nicotina) no NTS de ratos não anestesiados causou significante hipotensão e bradicardia que se mostrou dosedependente. Com a microinjeção unilateral do agonista colinérgico de receptor muscarínico (pilocarpina) no NTS observamos significante hipotensão e bradicardia, onde as doses maiores que 1 nmol/100 nL causaram hipotensão seguida de aumento da pressão arterial e bradicardia. A microinjeção unilateral do inibidor da nNOS (TRIM 13,3 nmol/100 nL) no NTS reduziu significantemente a hipotensão e bradicardia causadas pela nicotina e pilocarpina no NTS. O bloqueio da nNOS também reduziu significantemente o aumento de pressão arterial média causado pela microinjeção de pilocarpina na dose de 5 nmol/100 nL. Os resultados são a primeira evidência funcional, em animais não anestesiados, da participação de ambos os subtipos de receptores colinérgicos (nicotínico e muscarínico) na resposta da ACh no NTS. As diferenças observadas com a estimulação seletiva dos receptores colinérgicos no NTS sugerem a participação de cada subtipo de receptor na modulação da transmissão de estímulos cardiovasculares distintos, e, a função do sistema colinérgico sofre influência, ainda por meios desconhecidos, do óxido nítrico de origem central. / The Nucleus of the Solitary Tract is the first sites of cardiovascular reflex afferent terminations in the central nervous system (CNS). Acetylcholine (ACh) is present within neurons and terminals in the NTS and its participation in modulation of neurovegetative function was suggested since the 80´s. However, most part of the studies in literature was performed in vitro and there were no evidences in nonanesthetized rats. Previous studies of our laboratory showed that ACh microinjection into the NTS of non-anesthetized rats elicits dose-dependent hypotension and bradicardia; and NO from nNOS may have a role in modulating these responses. Peripheral blockade of cholinergic muscarinic receptors (i.v. injection of methylatropine) did not alter hypotension induced by microinjection of ACh into the NTS of non-anesthetized rats, indicating that the activation of cholinergic system in the NTS elicits reduction of the sympathetic component. In order to discriminate cardiovascular responses elicited by cholinergic receptors stimulation in the NTS, we performed the dose-response curves for selective agonists nicotine (NIC) and pilocarpine (PIL) microinjected into the NTS of non-anesthetized rats. In addition, we investigated whether inhibition of the nNOS in the NTS affects the responses caused by cholinergic agonists. Male Wistar rats were prepared according to the methodology of guide cannulas implantation in the direction of the NTS for microinjection in freely-moving rats; and recording of blood pressure in nonanesthetized rats. Unilateral nicotine microinjection in the NTS of non-anesthetized rats caused dose-dependent hypotension and bradicardia. Microinjection of the muscarinic agonist (pilocarpine) in the NTS of non-anesthetized rats elicited significant hypotension and bradicardia, and with doses higher than 1nmol/ 100 nL it was observed hypotension followed by an increased in arterial pressure, and bradicardia. Blockade of neuronal nitric oxide syntase (nNOS) (TRIM 13.3 nmol/ 100 nL), in the NTS, significantly reduced responses elicited by nicotine and pilocarpine. Microinjection of TRIM also inhibited the increase in arterial pressure elicited by PIL 5 nmol/ 100 nL. These results are the first functional evidence in non-anesthetized rats of cholinergic receptors participation in ACh transmission s in the NTS. Differences observed with selective stimulation of cholinergic receptors in the NTS suggest the participation of each receptor subtype in modulation of distinct pathways of stimulus of cardiovascular integration to the NTS. Finally, the physiological effects of cholinergic transmission in the NTS are still unclear and NO modulation of this system remains to be elucidated. / TEDE / BV UNIFESP: Teses e dissertações
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.unifesp.br:11600/9400 |
| Date | 25 March 2009 |
| Creators | Silva, Liana Gouveia da [UNIFESP] |
| Contributors | Universidade Federal de São Paulo (UNIFESP), Colombari, Eduardo [UNIFESP] |
| Publisher | Universidade Federal de São Paulo (UNIFESP) |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | 103 p. |
| Source | reponame:Repositório Institucional da UNIFESP, instname:Universidade Federal de São Paulo, instacron:UNIFESP |
| Rights | info:eu-repo/semantics/openAccess |
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