Development of autonomic dysfunction with intermittent hypoxia in a lean murine model

• A lean murine model was employed to track the development of autonomic dysfunction independent of obesity.
• Exposure to intermittent hypoxia and continuous infusion of glucose or saline over 4 days reduced baroreflex sensitivity.
• Intermittent hypoxia promoted sympathetic activity whereas hyperglycemia suppressed parasympathetic activity.
• Ultradian (12-h) rhythmicity was substantially suppressed in mice exposed to intermittent hypoxia.
• Intermittent hypoxia combined with hyperglycemia progressively adversely affected autonomic control independent of obesity.

Intermittent hypoxia (IH) has been previously shown in a lean murine model to produce sustained hypertension and reverse the diurnal variation of blood glucose (BG). Concomitant glucose infusion attenuated the hypertension but exacerbated the BG fluctuations. In this study, cardiovascular variability analysis was employed to track the development of autonomic dysfunction in mice exposed to room air (IA) or IH, in combination with saline or glucose infusion. Baroreflex sensitivity was found to decrease in all animals, except in the control group. Low-frequency power of pulse interval spectrum, reflecting vagal activity, decreased more rapidly in glucose relative to saline while low-frequency power of blood pressure, reflecting sympathetic activity, decreased more slowly in IH relative to IA. Ultradian (∼12 h) rhythmicity was substantially suppressed in IH groups. These findings suggest that IH acted to increase sympathetic activity while glucose infusion led to reduced parasympathetic activity. The combination of IH and hyperglycemia leads to progressively adverse effects on autonomic control independent of obesity.