Chronic apnea during REM sleep increases arterial pressure and sympathetic modulation in rats.

STUDY OBJECTIVES: Obstructive sleep apnea can induce hypertension. Apneas in REM may be particularly problematic: they are independently associated with hypertension. We examined the role of sleep stage and awakening on acute cardiovascular responses to apnea. In addition, we measured cardiovascular and sympathetic changes induced by chronic sleep apnea in REM sleep. METHODS: We used rats with tracheal balloons and electroencephalogram and electromyogram electrodes to induce obstructive apnea during wakefulness and sleep. We measured the electrocardiogram and arterial pressure by telemetry and breathing effort with a thoracic balloon. RESULTS: Apneas induced during wakefulness caused a pressor response, intense bradycardia, and breathing effort. On termination of apnea, arterial pressure, heart rate, and breathing effort returned to basal levels within 10 s. Responses to apnea were strongly blunted when apneas were made in sleep. Post-apnea changes were also blunted when rats did not awake from apnea. Chronic sleep apnea (15 days of apnea during REM sleep, 8 h/day, 13.8 ± 2 apneas/h, average duration 12 ± 0.7 s) reduced sleep time, increased awake arterial pressure from 111 ± 6 to 118 ± 5 mmHg (p < 0.05) and increased a marker for sympathetic activity. Chronic apnea failed to change spontaneous baroreceptor sensitivity. CONCLUSION: Our results suggest that sleep blunts the diving-like response induced by apnea and that acute post-apnea changes depend on awakening. In addition, our data confirm that 2 weeks of apnea during REM causes sleep disruption and increases blood pressure and sympathetic activity.

Cardiovascular responses induced by obstructive apnea are enhanced in hypertensive rats due to enhanced chemoreceptor responsivity.

Spontaneously hypertensive rats (SHR), like patients with sleep apnea, have hypertension, increased sympathetic activity, and increased chemoreceptor drive. We investigated the role of carotid chemoreceptors in cardiovascular responses induced by obstructive apnea in awake SHR. A tracheal balloon and vascular cannulas were implanted, and a week later, apneas of 15 s each were induced. The effects of apnea were more pronounced in SHR than in control rats (Wistar Kyoto; WKY). Blood pressure increased by 57±3 mmHg during apnea in SHR and by 28±3 mmHg in WKY (p<0.05, n = 14/13). The respiratory effort increased by 53±6 mmHg in SHR and by 34±5 mmHg in WKY. The heart rate fell by 209±19 bpm in SHR and by 155±16 bpm in WKY. The carotid chemoreceptors were then inactivated by the ligation of the carotid body artery, and apneas were induced two days later. The inactivation of chemoreceptors reduced the responses to apnea and abolished the difference between SHR and controls. The apnea-induced hypertension was 11±4 mmHg in SHR and 8±4 mmHg in WKY. The respiratory effort was 15±2 mmHg in SHR and 15±2 mmHg in WKY. The heart rate fell 63±18 bpm in SHR and 52±14 bpm in WKY. Similarly, when the chemoreceptors were unloaded by the administration of 100% oxygen, the responses to apnea were reduced. In conclusion, arterial chemoreceptors contribute to the responses induced by apnea in both strains, but they are more important in SHR and account for the exaggerated responses of this strain to apnea.