Changes in reactive oxygen species (ROS) in central respiratory centers with sustained hypoxia

Abstract

ROS are important for plasticity in chemoreceptors and respiratory motor neurons with acute and chronic intermittent hypoxia. Recent studies show ROS change with sustained hypoxia so we hypothesized ROS contribute to plasticity with chronic sustained hypoxia (CSH) in ventilatory acclimatization to hypoxia. To test this, we measured (1) ventilation (Vi) in conscious, unrestrained mice breathing 21% or 10% O2 using barometric pressure plethysmography, and (2) ROS levels in medullary respiratory centers by imaging dihydroethidium (DHE) fluorescence in fixed tissue sections obtained after 2 hr of DHE exposure in 4 groups of mice (n=3–5 each): normoxic control (CON) and CSH (PiO2 = 70 Torr, 7 days), treated with a superoxide scavenger (MnTMPyP 5 mg/kg ip) or saline for 10–13 days prior to study. DHE fluorescence was observed in neurons but not glia. CSH decreased ROS to 60–71% of CON in nucleus tractus solitarii and hypoglossal neurons (NTS and XII). MnTMPyP decreased ROS in NTS and XII by 37% in CON but only 6–12% in CSH. In CON, Vi increased with MnTMPyP. Vi increased with CSH as expected but was not changed by MnTMPyP. The results are consistent with ventilatory inhibition by ROS that are scavenged by MnTMPyP and decreased in CSH. Supported by NIH RO1 HL‐081823 and 1P01 HL 098053.