Nucleus tractus solitarii reactive oxygen species contribute to acute intermittent hypoxia‐induced long‐term facilitation of phrenic and splanchnic sympathetic nerve activity (686.26)

Abstract

Cardiorespiratory neural networks undergo alterations in function (plasticity) that are critical to homeostasis but can be deleterious, as in obstructive sleep apnea (OSA). AIH in rats (10X: 45 sec of 10% O2 every 5 min) mimics cardiorespiratory changes as in OSA; prolonged increases in ventilatory/phrenic and sympathetic activity (AIH‐LTF) and augmented hypoxia (Hx) responses post‐AIH. The nTS integrates and modulates primary cardiorespiratory input and undergoes plasticity in response to changes in afferent input, including to Hx. nTS ROS are increased by intermittent Hx and important for plasticity. We hypothesized that nTS ROS contribute to AIH‐LTF and augmented Hx responses post‐AIH. Bilateral microinjection of the antioxidant catalase (CAT, 500 U/ml; 60 nl) in the nTS prior to each Hx bout during AIH attenuated AIH‐LTF for both integrated phrenic amplitude and splanchnic sympathetic nerve activity (%Δ: PhrA, Con=152±58, n=9; CAT=27±19, n=6; SSNA, Con=51±6, n=9; CAT=34±7, n=8). CAT also diminished augmented Hx responses post‐AIH (%Δ vs. Hx1st: PhrA, Con=76±37; CAT=14±22; SSNA, Con=90±11; CAT=50±13). In separate animals, chronically decreasing nTS ROS by injecting a viral vector overexpressing human catalase (AdCAT) also attenuated AIH‐LTF (%Δ: PhrA, Con=77±23, n=8; AdCAT=‐21±15, n=4; SSNA, Con=27±8; AdCAT=1±17). Data suggest nTS ROS contribute to phrenic and sympathetic AIH‐LTF. HL98602Grant Funding Source: Supported by HL98602