Cardiovascular and respiratory profiles during the sleep–wake cycle of rats previously submitted to chronic intermittent hypoxia

Abstract

New Findings What is the central question of this study?Chronic intermittent hypoxia (CIH) causes increased arterial pressure (AP), sympathetic overactivity and changes in expiratory modulation of sympathetic activity. However, changes in the short‐term sleep–wake cycle pattern after CIH and their potential impact on cardiorespiratory parameters have not been reported previously. What is the main finding and its importance?Exposure to CIH for 10 days elevates AP in wakefulness and sleep but does not cause major changes in short‐term sleep–wake cycle pattern. A higher incidence of muscular expiratory activity was observed in rats exposed to CIH only during wakefulness, indicating that active expiration is not required for the increase in AP in rats submitted to CIH. Abstract Chronic intermittent hypoxia (CIH) increases arterial pressure (AP) and changes sympathetic–respiratory coupling. However, the alterations in the sleep–wake cycle after CIH and their potential impact on cardiorespiratory parameters remain unknown. Here, we evaluated whether CIH‐exposed rats present changes in their short‐term sleep–wake cycle pattern and in cardiorespiratory parameters. Male Wistar rats (∼250 g) were divided into CIH and control groups. The CIH rats were exposed to 8 h day−1 of cycles of normoxia (fraction of inspired O2 = 0.208, 5 min) followed by hypoxia (fraction of inspired O2 = 0.06, 30–40 s) for 10 days. One day after CIH, electrocorticographic activity, cervical EMG, AP and heart rate were recorded for 3 h. Plethysmographic recordings were collected for 2 h. A subgroup of control and CIH rats also had the diaphragm and oblique abdominal muscle activities recorded. Chronic intermittent hypoxia did not alter the time for sleep onset, total time awake, durations of rapid eye movement (REM) and non‐REM (NREM) sleep and number of REM episodes in the 3 h recordings. However, a significant increase in the duration of REM episodes was observed. The AP and heart rate were increased in all phases of the cycle in rats exposed to CIH. Respiratory frequency and ventilation were similar between groups in all phases, but tidal volume was increased during NREM and REM sleep in rats exposed to CIH. An increase in the incidence of active expiration during wakefulness was observed in rats exposed to CIH. The data show that CIH‐related hypertension is not caused by changes in the sleep–wake cycle and suggest that active expiration is not required for the increase in AP in freely moving rats exposed to CIH.

Active expiration and chronic intermittent hypoxia‐induced hypertension: A hypothesis that still breathes!

“…We also described the presence of active expiration in conscious, freely moving rats, but in that study we were not aware of the incidence of active expiration in the different phases of the sleep–wake cycle (Moraes et al., ). In our recent study (Bazilio, Bonagamba, Moraes, & Machado, ), which was the focus of the Viewpoint by O´Connor et al. (), we documented that the incidence of active expiration was higher in awake CIH‐exposed hypertensive rats than in control animals (11 versus 3% of all respiratory cycles during wakefulness), but it was not observed in non‐REM and REM sleep.…”

“…In our recent study by Bazilio et al. (), the incidence of active expiration was evaluated 1 day after the 10 day CIH protocol. Therefore, the presence of active expiration and the enhancement of the expiratory modulation of sympathetic activity in the different phases of the sleep–wake cycle might be essential to establish the sympathetic overactivity and hypertension during the early part of the 10 day CIH protocol, but it might not be a requirement for the maintenance of this autonomic dysfunction.…”

Chronic intermittent hypoxia‐induced hypertension: An expired hypothesis laid to rest?

“…In this issue of Experimental Physiology , Bazilio, Bonagamba, Moraes, and Machado () present new and interesting findings extending this line of enquiry. The authors queried whether exposure to CIH evokes alterations in the sleep–wake cycle explicitly during the experimental period of blood pressure determination.…”

“…Although consideration of potentiated respiratory–sympathetic coupling as a potentially dominant contributor to CIH‐induced hypertension may now have expired, the study by Bazilio et al. () nevertheless breathes new life into the continued search for a comprehensive understanding of the mechanisms driving cardiovascular malady after exposure to CIH modelling OSAS.…”

Reply: The two faces of active expiration: a case of mistaken identity!

“…We drew focus in our viewpoint (O'Connor, Lucking & O'Halloran, ) to the persistent expression of hypertension across the sleep–wake cycle in animals exposed to chronic intermittent hypoxia (CIH), with evidence of active expiration only in wakefulness (Bazilio, Bongamba, Moraes & Machado, ). Our intent was to emphasize that active expiration, defined as the motor recruitment of abdominal muscles in support of enhanced pulmonary ventilation, was not obligatory for the continued manifestation of high blood pressure following exposure to CIH.…”