Modificações ventilatórias induzidas pela hipóxia intermitente aguda em condições não anestesiadas

• Autor(a) principal: Mendonça Junior, Bolival Apparecido
• Data de Publicação: 2020
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFSCAR
• Texto Completo: https://repositorio.ufscar.br/handle/ufscar/13253
• topic: Expiração ativa; Não-anestesiado; Serotonina; Núcleo retrotrapezóide; Facilitação de longo prazo; Active expiration; Non-anesthetized; Serotonin; Retotrapezoid nucleus; Long-term facilitation; CIENCIAS BIOLOGICAS::FISIOLOGIA

It has been described that intermittent hypoxia (IH, periods of hypoxia followed by normoxia), as observed in some pathological situations, promotes, acutely, a sustained increase in respiratory motor activity, dependent on the release of serotonin in areas of the central nervous system (brainstem and spinal cord). This effect has been demonstrated mostly in vagotomized and anesthetized animal preparations, which exhibited a potentiation of inspiratory and expiratory motor activities in response to acute IH (AIH). Evidence about the effects of AIH on respiratory activity in non-anesthetized conditions is scarce, especially considering the possible changes in the partial pressure of blood gases and body temperature that might follow such respiratory changes. In the present study, we found that pulmonary ventilation of unanesthetized Holtzman rats (80-150g, n = 9) submitted to 10 cycles of AIH (6% O2 for 30-40 s, every 5 minutes) was elevated compared to control animals (maintained in normoxia, n = 13), due to a long-lasting increase in tidal volume (P <0.05), but not in respiratory frequency, which peaked 30 minutes after the last hypoxia exposure. AIH-treated rats also exhibited increased expiratory flow events during the second stage of the expiratory phase, indicating the presence of active expiratory pattern (events not seen in control animals). The compensatory increase in ventilation and active expiration elicited by AIH were associated with reduced arterial partial pressure of CO2 (PaCO2, n = 5) and a significant reduction in body temperature (n = 6, P <0.05). The pre-treatment with the antagonist for serotonin type 2 receptor (5-HT2), ketanserin (1 mg/kg, i.p.), was able to prevent the ventilatory changes induced by AIH, the emergence of active expiration (n = 11) and the reduction in PaCO2 (n = 5). On the other hand, ketanserin treatment potentiated the AIH-mediated response of the reduction in body temperature (n = 5, P <0.05). Moreover, we verified that the generation of active expiration after AIH was not associated with the phosphorylation of AMPA glutamate receptors (n = 3 / group) in the retotrapezoid nucleus – a brainstem region related to the generation of active expiration – thus demonstrating that it might occur through other mechanisms. Our findings indicate that AIH, in unanesthetized conditions, promotes a long-term increase in pulmonary ventilation associated with changes in the breathing pattern (generation of active expiration) and changes in body temperature. Such respiratory modifications are associated with the recruitment of serotonergic signaling, while a decrease in body temperature that does not require the activation of 5-HT2 receptors.