Airway obstruction produces widespread sympathoexcitation: role of hypoxia, carotid chemoreceptors, and NTS neurotransmission

Obstructive sleep apnea (OSA) is the most common respiratory disturbance of sleep and is closely associated to cardiovascular diseases. In humans, apnea increases respiratory effort and elevates muscle sympathetic nerve activity (SNA), but the primary stimulus for the SNA activation has not been ide...

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Detalles Bibliográficos
Autores: Ferreira, Caroline B. [UNIFESP], Cravo, Sergio L. [UNIFESP], Stocker, Sean D.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:Brasil
Institución:Universidade Federal de São Paulo (UNIFESP)
Repositorio:Repositório Institucional da UNIFESP
Idioma:inglés
OAI Identifier:oai:repositorio.unifesp.br:11600/54198
Acceso en línea:http://dx.doi.org/10.14814/phy2.13536
https://repositorio.unifesp.br/handle/11600/54198
Access Level:acceso abierto
Palabra clave:Apnea
carotid chemoreceptors
NTS
sympathetic nerve activity
Descripción
Sumario:Obstructive sleep apnea (OSA) is the most common respiratory disturbance of sleep and is closely associated to cardiovascular diseases. In humans, apnea increases respiratory effort and elevates muscle sympathetic nerve activity (SNA), but the primary stimulus for the SNA activation has not been identified. We recently developed a model of apnea in rodents using acute airway obstruction. In this study, we employed this model to test whether the elevation in SNA was mediated by hypoxia, carotid chemoreceptors, or neurotransmission in the nucleus tractus solitarius (NTS). In anesthetized, male Sprague-Dawley rats, airway obstruction (20s) increased phrenic nerve activity (PNA), arterial blood pressure (ABP), and lumbar, renal, and splanchnic SNA. The changes in SNA were similar across all three sympathetic nerves. Inactivation of chemoreceptors by hyperoxia (100% O-2) or surgical denervation of carotid chemoreceptors attenuated, but did not eliminate, the changes in SNA and ABP produced by airway obstruction. To interrupt afferent information from carotid chemoreceptor and extracarotid afferents to the hindbrain, airway obstruction was performed before and after NTS microinjection of the GABA(A) agonist muscimol or a cocktail of NMDA and non-NMDA antagonists. Inhibition of NTS neurons or blockade of glutamatergic receptors attenuated the increase in lumbar SNA, splanchnic SNA, renal SNA, and PNA. Collectively, these findings suggest that PNA and SNA responses induced by airway obstruction depend, in part, on chemoreceptors afferents and glutamatergic neurotransmission in the NTS.