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Previous issue date: 2013-08-26 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / The nucleus of the solitary tract (NTS) is the primary synaptic site of the
peripheral baroreceptors and chemoreceptors. It has been shown that acetylcholine
(ACh) microinjected into the NTS of rats induces hypotension and bradycardia.
However, the contribution of cholinergic mechanisms at different NTS subnuclei
(intermediate and commissural) as well as the cholinergic receptors blockade on the
control of sympathetic (SNA) and phrenic (PNA) nerve activities have not been
studied yet. In this study we assessed the role of ACh and its cholinergic receptors at
the intermediate NTS (iNTS) and commissural NTS (cNTS) on the control of SNA,
PNA and electrophysiological properties of these subnuclei neurons, as well as on
baro and chemoreflex responses. Decorticated arterially-perfused in situ preparations
of male juvenile rats were used to record SNA and PNA. Microinjections of ACh and
cholinergic antagonists were performed into the iNTS or cNTS. Coronal slices of the
brainstem containing either cNTS or iNTS subnuclei were obtained from male
juvenile rats and used in whole cell patch clamp – current clamp recordings. It was
observed that ACh microinjected into the iNTS inhibited both SNA and PNA. These
effects were reduced by the pre-treatment with atropine (muscarinic antagonist) or
mecamylamine (nicotinic antagonist). The cholinergic antagonists into the iNTS did
not change the effects on SNA and PNA induced by baro and chemoreflex activation.
In contrast, microinjections of ACh into the cNTS did not induce changes in SNA, but
increased PNA. Despite the absence of changes in SNA, ACh into the cNTS
changed the pattern of respiratory-sympathetic coupling. Both atropine and
mecamylamine into the cNTS inhibited the ACh-induced tachypnea, but only
mecamylamine inhibited the chemoreflex-induced tachypnea and the ACh-induced
change in respiratory-sympathetic coupling. In vitro studies demonstrated that ACh
promotes depolarization in both iNTS and cNTS neurons. Both muscarinic and
nicotinic antagonism in the iNTS inhibited the ACh-induced depolarization. However,
only nicotinic antagonist was effective in diminishing this response in the cNTS. The
results suggest that ACh plays an important role in the control of cardiovascular and
respiratory activities, with distinct functions between iNTS and cNTS. This cholinergic
control involves activation of both muscarinic and nicotinic receptors within NTS, but
only nicotinic receptors are involved in the chemoreflex tachypneic response. / O núcleo do trato solitário (NTS) é o sítio primário de aferências dos
barorreceptores arteriais e quimiorreceptores. Sabe-se que a acetilcolina (ACh)
injetada no NTS de ratos provoca hipotensão e bradicardia. Entretanto, não se sabe
até o momento qual o papel do sistema colinérgico nos diferentes subnúcleos do
NTS (intermediário ou comissural) ou o bloqueio de seus receptores na atividade
simpática (SNA) ou na atividade do frênico (PNA). No presente estudo avaliamos os
efeitos da ACh e seus receptores no NTS intermediário (NTSi) e comissural (NTSc)
sobre a SNA, PNA e sobre as propriedades eletrofisiológicas dos neurônios desses
subnúcleos, bem como nas respostas do baro e quimiorreflexos. Preparações in situ
decorticadas de ratos jovens foram utilizadas para registro da SNA e PNA, e ACh e
antagonistas colinérgicos foram microinjetados no NTSi ou NTSc. Cortes coronais
bulbares contendo o NTSi ou NTSc foram obtidos de ratos jovens e utilizados para
registro de neurônios através da técnica whole cell patch clamp – current clamp. Foi
observado que a microinjeção de ACh no NTSi inibe tanto a SNA quanto a PNA,
sendo que tais efeitos são inibidos pelo tratamento com atropina (antagonista
muscarínico) ou mecamilamina (antagonista nicotínico). Os antagonistas colinérgicos
no NTSi não alteraram os efeitos na SNA e PNA induzidos pela ativação do baro e
quimiorreflexos. Por outro lado, microinjeções de ACh no NTSc não altera a SNA
mas promove aumento da PNA. Apesar de não alterar a SNA, a ACh no NTSc
promove alterações no acoplamento simpato-respiratório. Tanto a atropina quanto a
mecamilamina microinjetadas no NTSc inibiram a taquipnéia induzida pela ACh, mas
apenas a mecamilamina inibiu a taquipnéia resultante do quimiorreflexo e a
alteração no acoplamento simpato-respiratório induzida pela ACh no NTSc. Nos
estudos in vitro, observamos que a ACh promove respostas de despolarização em
neurônios tanto do NTSi quanto do NTSc. O bloqueio de receptores tanto nicotínicos
quanto muscarínicos no NTSi diminui a despolarização evocada pela ACh. No
entanto, apenas o antagonista nicotínico foi capaz de diminuir essa resposta no
NTSc. Os resultados sugerem que a ACh desempenha um importante papel no
controle cardiorrespiratório, com funções distintas entre NTSi e NTSc. Esse controle
colinérgico envolve a ativação de receptores tanto nicotínicos quanto muscarínicos
no NTS, mas apenas receptores nicotínicos estão envolvidos na resposta de
taquipnéia do quimiorreflexo. / FAPESP: 2010/17218-0
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufscar.br:ufscar/8981 |
| Date | 26 August 2013 |
| Creators | Furuya, Werner Issao |
| Contributors | Colombari, Débora Simões de Almeida, Zoccal, Daniel Breseghello |
| Publisher | Universidade Federal de São Carlos, Câmpus São Carlos, Programa de Pós-graduação em Ciências Fisiológicas, UFSCar |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Source | reponame:Repositório Institucional da UFSCAR, instname:Universidade Federal de São Carlos, instacron:UFSCAR |
| Rights | info:eu-repo/semantics/openAccess |
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