Acute Hypoxia (AH) Potentiates Cardiorespiratory Responses to Blockade of the Anti‐oxidant Enzyme, Glutathione Peroxidase (GPX), in the Nucleus Tractus Solitarius (nTS)

Abstract

AH in conscious rats activates the arterial chemoreflex and increases reactive oxygen species (ROS) in the nTS. We previously showed that mRNA for the anti‐oxidant enzyme GPX in the nTS is increased with AH (10% O2, 2 hr), possibly as an early protective response to AH. Current experiments evaluated effects of AH on cardiorespiratory responses to GPX blockade in the nTS with mercaptosuccinic acid (MCS). Mean arterial pressure (MAP), heart rate (HR), and splanchnic sympathetic & phrenic nerve activities (SSNA; PhNA) were measured in anesthetized (inactin, 100 mg/kg), paralyzed (gallamine, 25 mg/kg/hr), artificially ventilated, vagotomized male rats. Increasing concentrations of MCS (0.05, 0.1, and 0.5M) were microinjected (30 nl) into the nTS before (MCS‐1) and after (MCS‐2) 4 evenly spaced bouts (5 min) of hypoxia (O2 saturation ~50%) over a 2 hr period. SSNA and PhNA were expressed as % baseline before MCS‐1. In rats exposed to AH, compared to time controls (no hypoxic stimuli), baseline values increased between MCS‐1 and MCS‐2: HR (+29± 5 vs +1± 3 bpm), SSNA (+43± 8 vs +5± 8%), overall PhNA (+47± 24 vs ‐3± 2 %) and Ph amplitude (+112± 27 vs +26± 32%). Increasing concentrations of MCS progressively decreased MAP, HR, SSNA, and PhNA (rate and amplitude) in all rats. However, responses to GPX blockade in the nTS were augmented following AH (ΔMCS‐2 > ΔMCS‐1): Maximum ΔMAP (‐39± 2 > ‐33± 2 mm Hg); ΔSSNA (‐113± 9 > ‐80± 2 %); ΔPhNA (‐94± 19 > ‐ 38± 8 %). Thus, consistent with increased mRNA for GPX, cardiorespiratory effects of GPX in the nTS appear to be augmented following AH. [NIH HL 98602]