Diurnal Variations in Acute Intermittent Hypoxia-induced Sympathetic Long-term Facilitation

Acute intermittent hypoxia (AIH) elicits neuroplasticity in both the respiratory ( e.g., phrenic long-term facilitation; or pLTF) and sympathetic nervous systems (sympathetic LTF; or sympLTF). pLTF and sympLTF are expressed as sustained increases in phrenic or sympathetic neural activity lasting hours after return to control oxygen levels. Although our understanding of factors regulating pLTF has advanced considerably, relatively little is known concerning factors regulating sympLTF. In recent years, AIH has been explored as a treatment to restore respiratory, upper airway, limb and cardiovascular function in people living with spinal cord injury and neuromuscular disease. In this translational process, it is important to consider time-of-day, particularly when comparing nocturnal rodents, which are typically studied in their rest phase, versus diurnal humans studied in their active phase. Although we recently demonstrated that the magnitude and mechanism of AIH-induced pLTF varies between the rat’s active vs rest phase (with a greater magnitude in the rest phase), virtually nothing is known concerning rest/active phase differences in sympLTF. To address this knowledge gap, we tested the hypothesis that AIH elicits greater sympLTF during the rat's mid-rest versus mid-active phase. We assessed sympLTF by recording renal SNA (RSNA) in anesthetized, paralyzed, and ventilated male Sprague-Dawley rats in the mid-rest and mid-active phases (n=7 per group). Rats were exposed to moderate AIH (arterial PO 2 ~ 40-55 mmHg) consisting of 15, one-minute episodes of isocapnic hypoxia (baseline arterial PCO 2 ~40-42 mmHg), interspersed with 90 second intervals of control oxygen conditions. Baseline RSNA activity (volts) did not differ between mid-rest and mid-active phase (mid-rest: 0.06±0.02; mid-active: 0.08±0.01; P=0.629). On the other hand, a greater post-AIH increase in RSNA was observed during the mid-rest (ΔRSNA: 83±24%) versus mid-active phase at 90 minutes post-AIH (26±9%; P=0.031). While mechanisms underlying this time-of-day effect are not yet known, these findings provide valuable insight concerning the influence of timing on AIH-induced sympLTF in healthy rats. This foundational understanding will inform future studies aimed at elucidating the impact of spinal cord injury or neurologic disease on neuroplasticity in the sympathetic nervous system. Supported by: NIH R01HL147554 & R01HL148030 (G.S. Mitchell) and NIH F32HL176048 (A.L.E. Butenas) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.