Chronic intermittent hypoxia increases airway hyperresponsiveness during house dust mites exposures in rats

Abstract

Introduction Accumulating clinical evidence links Obstructive Sleep Apnea (OSA) with worse outcomes of asthma, but impact on airway function remains sparsely studied. We tested effects of Chronic Intermittent Hypoxia (CIH) – a hallmark of OSA – on airway hyperresponsiveness (AHR), in a rat model of chronic allergen-induced inflammation. Methods Brown Norway rats were exposed to six weeks of CIH or normoxia (NORM) concurrent with weekly house dust mites (HDM) or saline (SAL) challenges. At endpoint, we assessed responses to seven Methacholine (Mch) doses (0, 4, 8, 16, 32, 64, 128 mg/mL) on a FlexiVent system (Scireq). Maximal (or plateau) responses (reactivity) for total respiratory system Resistance (Rrs) and Elastance (Ers), Newtonian airway resistance (RN, a measure of central airways function) and tissue damping (G, a measure of distal airways function) were plotted. Results HDM/CIH–treated animals demonstrated the highest reactivity to Mch in Rrs and Ers compared to all other groups (HDM/NORM, SAL/CIH and SAL/NORM p < 0.05 for all comparisons, for doses 5–7 for Rrs, and for doses 4–7 for Ers). The enhanced Rrs response was due to an increase in G (doses 4–7, p < 0.05 for comparisons to all other groups), whereas RN was not affected by CIH. Conclusions In rats chronically challenged with HDM, concurrent CIH exposure induces AHR primarily in the distal airways, which affects the respiratory system frequency-dependent elastic properties.

Adipocyte-derived exosomes from obstructive sleep apnoea rats aggravate MASLD by TCONS_00039830/miR-455-3p/Smad2 axis

“…Third, OSA is caused by respiratory abnormalities, whereas the model in the present study was induced by exposure to reduced oxygen concentrations. Although the OSA modelling based on chronic intermittent hypoxia has been widely used in multiple studies 41 – 43 , a suitable model for OSA is needed to verify the significance of the TCONS_00039830/miR-455-3p/ Smad2 axis in OSA and MASLD.…”

“…Chronic intermittent hypoxia (CIH) was used to construct an OSA model in this study. The induction principle of OSA-related diseases including MASLD was caused by chronic hypoxia caused by OSA 41 – 43 . OSA could directly cause a decrease in oxygen inhalation.…”

“…The intermittent low O 2 concentration was provided by keeping the average O 2 concentration at 10 ± 1% for 60 s (hypoxia phase) and then raised to 20–21% for 30 s (normal phase). OSA models were constructed by maintaining the rats under intermittent low O 2 concentration for 8 h/day (9:00 am to 5:00 pm) for 6 weeks 41 – 43 . The 24 rats of MASLD model were randomly divided into four groups, namely MASLD, MASLD + OSA-Exo, MASLD + miR-455-3p and MASLD + miR-455-3p + OSA-Exo groups.…”

Exosomes regulate SIRT3-related autophagy by delivering miR-421 to regulate macrophage polarization and participate in OSA-related NAFLD

“…In this study, chronic intermittent hypoxia (CIH) was used to construct an OSA model. The induction principle of OSA-related diseases, including metabolic dysfunction-associated steatotic liver disease, was based on OSA-induced chronic hypoxia [ 21 – 23 ]. OSA could decrease O 2 inhalation directly.…”

Revisiting Asthma Obstructive Sleep Apnea Overlap: Current Knowledge and Future Needs

“…In sheep, bronchial responsiveness to methacholine was increased by hypoxia and the response was mediated by carotid body chemoreceptors [90]. Teodorescu and colleagues showed that chronic intermittent hypoxia increased airway hyperresponsiveness to methacholine challenge in rats exposed to house dust mites and intermittent hypoxia [91]. Intermittent hypoxia for 6 h/d for 14 days increased methacholine-induced airway hyperresponsiveness and inflammatory marks in bronchoalveolar fluid in rats [92].…”