Differential cardiovascular and autonomic responses to structurally distinct intermittent hypoxia paradigms in rats

Intermittent hypoxia (IH), the key physiological stressor in obstructive sleep apnea, is commonly quantified by respiratory event frequency. However, clinical heterogeneity in hypertension among patients with comparable apnea-hypopnea index (AHI) suggests that episode timing, including the duration and frequency of desaturation-reoxygenation cycles, may exert distinct biological effects even under equal cumulative burden. To test this, male Wistar-Kyoto rats were exposed for 21 days (8 h/day) to IH with either 10-s hypoxia duration at 30 cycles/h (10s-30c) or 5-s hypoxia duration at 60 cycles/h (5s-60c), while room air served as a control. Cardiovascular regulation was evaluated by continuous measurement of mean arterial pressure, heart-rate variability, and baroreflex sensitivity, and broader systemic effects were assessed through sleep-wake architecture, EEG activity, spatial memory, and cortical/hippocampal protein markers. Both IH groups had elevated blood pressure and disrupted autonomic balance compared with controls. The 5s-60c group produced more sustained hypertension, blunted nocturnal dipping, greater baroreflex impairment, and enhanced beta power during sleep, indicating persistent sympathetic drive. By contrast, the 10s-30c group was associated with increased paradoxical sleep, impaired spatial memory, reduced NeuN expression, and stronger upregulation of IBA-1 and NF-κB. These findings demonstrate that equivalent cumulative hypoxic exposure with different temporal structures yields divergent cardiovascular and neurocognitive outcomes. High-frequency, short-duration episodes preferentially promoted cardiovascular dysregulation, whereas longer episodes were linked to neurocognitive vulnerability. Consideration of hypoxic episode duration may improve the mechanistic interpretation of cardiovascular heterogeneity associated with sleep-disordered breathing.