Chronic intermittent hypoxia (CIH, 3d) attenuates glutathione peroxidase expression (Gpx1) and function in the caudal nucleus tractus solitarii (cnTS)

Abstract

Hypoxia increases reactive oxygen species (ROS) in the nTS which likely contribute to changes in cardiorespiratory control. Previously we reported that 2 h of acute hypoxia increased mRNA for the ROS inactivating enzyme Gpx1 in the nTS. Current experiments evaluated GPX in CIH (3d). Gpx1 mRNA in the cnTS trended to decrease in 6 CIH (0.6 ± 0.1) versus 6 normoxic (N) male rats (1.0 ± 0.3). In inactin anesthetized, neuromuscular blocked, artificially ventilated and vagotomized N (6) and CIH rats (5), baseline cardiorespiratory values were similar. Microinjection of mercaptosuccinic acid (MCS, 30 nl; 0.05, 0.1, 0.5M), a GPX antagonist, in the cnTS produced similar graded responses. At 0.5M, MCS eliminated phrenic nerve discharge, and decreased mean arterial pressure ( N = −50 ± 5; CIH = −45 ± 5 mmHg) and heart rate ( N = −50 ± 5; CIH = −39 ± 9 bpm). However, decreases in splanchnic sympathetic nerve activity due to 0.5M MCS were attenuated in CIH (−68 ± 8%) versus N rats (−87± 4%), consistent with decreased Gpx1 mRNA. Data suggest that an initial compensatory increase in Gpx1 mRNA is reversed following 3 d CIH possibly contributing to attenuated sSNA responses to GPX blockade. NIH HL 98602