Abstract
Autonomic dysfunction is involved in the development of hypertension in humans with obstructive sleep apnea, and animals exposed to chronic intermittent hypoxia (CIH). It has been proposed that a crucial step in the development of the hypertension is the potentiation of the carotid body (CB) chemosensory responses to hypoxia, but the temporal progression of the CB chemosensory, autonomic and hypertensive changes induced by CIH are not known. We tested the hypothesis that CB potentiation precedes the autonomic imbalance and the hypertension in rats exposed to CIH. Thus, we studied the changes in CB chemosensory and ventilatory responsiveness to hypoxia, the spontaneous baroreflex sensitivity (BRS), heart rate variability (HRV) and arterial blood pressure in pentobarbital anesthetized rats exposed to CIH for 7, 14, and 21 days. After 7 days of CIH, CB chemosensory and ventilatory responses to hypoxia were enhanced, while BRS was significantly reduced by 2-fold in CIH-rats compared to sham-rats. These alterations persisted until 21 days of CIH. After 14 days, CIH shifted the HRV power spectra suggesting a predominance of sympathetic over parasympathetic tone. In contrast, hypertension was found after 21 days of CIH. Concomitant changes between the gain of spectral HRV, BRS, and ventilatory hypoxic chemoreflex showed that the CIH-induced BRS attenuation preceded the HRV changes. CIH induced a simultaneous decrease of the BRS gain along with an increase of the hypoxic ventilatory gain. Present results show that CIH-induced persistent hypertension was preceded by early changes in CB chemosensory control of cardiorespiratory and autonomic function.
Highlights
Obstructive sleep apnea (OSA), a highly prevalent sleep-breathing disorder is recognized as an independent risk factor for systemic diurnal hypertension (Gozal and Kheirandish-Gozal, 2008; Somers et al, 2008; Dempsey et al, 2010)
MABP, mean arterial blood pressure; HR, heart rate; VT, tidal volume; fR, respiratory rate; V, minute inspiratory volume; fx, frequency of carotid chemosensory discharges measured in normoxia (PO2 ∼ 150 ± 10 mm Hg). *P < 0.05; **P < 0.01 chronic intermittent hypoxia (CIH) groups vs. Sham group; Neuman-Keuls post-hoc test after One-Way
We found that CIH-treated rats after 7 days display a marked reduction in the baroreflex sensitivity (BRS) compared to the the changes in the low frequency (LF)/high frequency (HF) spectral index of heart rate variability (HRV)
Summary
Obstructive sleep apnea (OSA), a highly prevalent sleep-breathing disorder is recognized as an independent risk factor for systemic diurnal hypertension (Gozal and Kheirandish-Gozal, 2008; Somers et al, 2008; Dempsey et al, 2010). Among all the disturbances produced by OSA, the chronic intermittent hypoxia (CIH) is considered the main factor for the development of hypertension (Gozal and Kheirandish-Gozal, 2008; Somers et al, 2008; Dempsey et al, 2010). The pathogenic mechanisms involved in the development of hypertension have been extensively studied in animal models of CIH, which simulate the hypoxic-reoxygenation cycles observed in OSA patients and reproduce the main cardiovascular
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