Increased sympathetic outflow in juvenile rats submitted to chronic intermittent hypoxia correlates with enhanced expiratory activity

Abstract

Chronic intermittent hypoxia (CIH) in rats produces changes in the central regulation of cardiovascular and respiratory systems by unknown mechanisms. We hypothesized that CIH (6% O 2 for 40 s, every 9 min, 8 h day −1 ) for 10 days alters the central respiratory modulation of sympathetic activity. After CIH, awake rats (n = 14) exhibited higher levels of mean arterial pressure than controls (101 ± 3 versus 89 ± 3 mmHg, n = 15, P < 0.01). Recordings of phrenic, thoracic sympathetic, cervical vagus and abdominal nerves were performed in the in situ working heart-brainstem preparations of control and CIH juvenile rats. The data obtained in CIH rats revealed that: (i) abdominal (Abd) nerves exhibited an additional burst discharge in late expiration; (ii) thoracic sympathetic nerve activity (tSNA) was greater during late expiration than in controls (52 ± 5 versus 40 ± 3%; n = 11, P < 0.05; values expressed according to the maximal activity observed during inspiration and the noise level recorded at the end of each experiment), which was not dependent on peripheral chemoreceptors; (iii) the additional late expiratory activity in the Abd nerve correlated with the increased tSNA; (iv) the enhanced late expiratory activity in the Abd nerve unique to CIH rats was accompanied by reduced post-inspiratory activity in cervical vagus nerve compared to controls. The data indicate that CIH rats present an altered pattern of central sympathetic-respiratory coupling, with increased tSNA that correlates with enhanced late expiratory discharge in the Abd nerve. Thus, CIH alters the coupling between the central respiratory generator and sympathetic networks that may contribute to the induced hypertension in this experimental model.

Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats

“…42,43 The hypertension induced by CIH is associated with reduced BRS efficiency in adult animals exposed to CIH for 1 to 3 months, 9,[11][12][13][14]40,41,44 but other studies performed in juvenile rats have shown that juvenile rats exposed to CIH for 15 days showed an increased cardiac baroreflex gain associated with a rightward shift on the operating point to higher pressures, as related to control rats. 38 Zoccal et al 38 proposed that the sympathetic-mediated hypertension is not secondary to a reduction in cardiac baroreflex gain, but to an enhanced respiratory-sympathetic coupling. As abovementioned, previous studies performed in adult rats 9,44 exposed to CIH clearly evidenced a significant impairment of the cardiac baroreflex.…”

“…16,17,36,37 Similarly, animal exposed to CIH show sympathetic hyperactivity and develop systemic hypertension. [8][9][10]13,18,19,38 The autonomic dysfunction is associated with a reduction of BRS and changes in HRV in patients with OSA 37,39 and animals exposed to CIH. 9,[12][13][14]40,41 Interaction of chemo-and baroreflexes plays a main role in the cardiorespiratory and autonomic homeostasis.…”

Oxidative Stress in the Carotid Body: Implications for the Cardioventilatory Alterations Induced by Obstructive Sleep Apnea

“…The hypoxic-reoxygenation episodes in OSA patients enhance the cardiorespiratory and sympathetic responses to acute hypoxia (Carlson et al, 1993;Narkiewicz et al, 1998aNarkiewicz et al, , 1998bNarkiewicz et al, , 1999; impair the autonomic regulation of the heart rate and the arterial blood pressure (Narkiewicz et al, 1999b, Shiomi et al, 1996 and exacerbate the renin-angiotensin system (Fletcher et al, 2002, Moller et al, 2003. Similarly, animals exposed to intermittent hypoxia show potentiated sympathetic discharges and vascular responses to hypoxia, and develop systemic hypertension (Dick et al, 2007;Fletcher et al, 1992, Greenberg et al, 1999, Zoccal et al, 2008. The autonomic hyperactivity is associated with a reduction of the efficiency of the baroreflex control of heart rate and alterations of heart rate variability in OSA patients (Narkiewicz et al, 1998b, Shiomi et al, 1996 and animals exposed to intermittent hypoxia (Lai et al, 2006;Lin et al, 2007;Rey et al, , 2008.…”

Contribution of Autonomic Nervous System to the Hypertension Induced by Obstructive Sleep Apnea

“…OSA patients with elevated NE levels in plasma and urine showed severe hypertension and excessive sweating, similar to what happened in pheochromocytoma, improved their condition with CPAP therapy ( [36]. It has also been shown that CPAP reduces NE levels in patients with severe OSA [101,113,114]. In children with OSA an association between AHI and urinary NE and E has been also reported [76].…”

“…OSA patients showed increased sympathetic and reduced vagal modulation of HRV in comparison with controls [2,4]. This symphato-vagal imbalance is modified with CPAP therapy; in OSA patients with hypertension CPAP administration reduced the LF power [11,114].…”