Chronic intermittent hypoxia enhances cat chemosensory and ventilatory responses to hypoxia

Abstract

The carotid body (CB) chemoreceptors may play an important role in the enhanced hypoxic ventilatory response induced by chronic intermittent hypoxia (CIH). We studied the effects of cyclic hypoxic episodes of short duration on cat cardiorespiratory reflexes, heart rate variability, and CB chemosensory activity. Cats were exposed to cyclic hypoxic episodes (P O 2 ∼ 75 Torr) repeated during 8 h for 2-4 days. Cats were anaesthetized with sodium pentobarbitone (40 mg kg −1 I.P., followed by 8-12 mg I.V.), and ventilatory and cardiovascular responses to NaCN (0.1-100 µg kg −1 I.V.) and several isocapnic levels of oxygen (P O 2 ∼ 20-740 Torr) were studied. After studying the reflex responses, we recorded the CB chemosensory responses induced by the same stimuli. Results showed that CIH for 4 days selectively enhanced cat CB ventilatory (V T and V I ) responses to hypoxia, while responses to NaCN remained largely unchanged. Similarly, basal CB discharges and responses to acute hypoxia (P O 2 < 100 Torr) were larger in CIH than in control cats, without modification of the responses to NaCN. Exposure to CIH did not increase basal arterial pressure, heart rate, or their changes induced by acute hypoxia or hyperoxia. However, the spectral analysis of heart rate variability of CIH cats showed a marked increase of the low-/high-frequency ratio and an increase of the power spectral distribution of low frequencies of heart rate variability. Thus, the enhanced CB reactivity to hypoxia may contribute to the augmented ventilatory response to hypoxia, as well as to modified heart rate variability due to early changes in autonomic activity.

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

“…enhances CB chemosensory discharge in normoxia and in response to hypoxia. 12,19,[23][24][25] Furthermore, it has been shown that arterial blood pressure (BP) rapidly increases after 3 to 4 days after CIH exposure, 14,[26][27][28] which is consistent with the time required to potentiate the neural discharges from the CB chemoreceptor during CIH .…”

“…12,13,19,30 In addition, we studied the effects of the β-adrenergic and cholinergic receptors blockers on resting HR to determine the sympathovagal control to the heart.…”

“…enhances CB chemosensory discharge in normoxia and in response to hypoxia. 12,19,[23][24][25] Furthermore, it has been shown that arterial blood pressure (BP) rapidly increases after 3 to 4 days after CIH exposure, 14,[26][27][28] which is consistent with the time required to potentiate the neural discharges from the CB chemoreceptor during CIH .19,24 Despite all the advances related to the contribution of CB chemoreception to the cardiovascular consequences of CIH, there are no studies showing the role played by the CB chemoreflex once the hypertensive phenotype has become expressed because of CIH exposure. It is worth noting that it is fundamental from a translational perspective because in previous studies performed by Fletcher et al,20 the CBs were removed before the start of CIH and, therefore, before the development of 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. It is well known that hypoxic chemoreflex activation evokes baroreflex inhibition attributed to central nervous system modulation at the level of the nucleus of the solitary tract.…”

“…[8][9][10][11][12][13][14] Although the link between OSA and hypertension is well established, the mechanisms responsible for the autonomic imbalance and the hypertension are not entirely known. CIH produces oxidative stress, inflammation, and endothelial dysfunction that contribute to the hypertension.…”