The sympathetic nervous system and catecholamines metabolism in obstructive sleep apnoea

Abstract

Obstructive sleep apnoea (OSA) is the most common sleep disorder of breathing in middle-aged and overweight subjects. It features recurrent episodes of upper airway total (apnoea) o partial (hypopnea) collapse during sleep, which are associated with a reduction in blood oxygen saturation and with arousal from sleep to re-establish airway patency. An association of OSA with dysregulation of the autonomous nervous system (ANS) and altered catecholamines (CAs) metabolism has been contended for years. However, the pathophysiology mechanisms underlying these alterations remain to be fully clarified. Nonetheless, these alterations are deemed to play a key pathogenic role in the established association of OSA with several conditions besides arterial hypertension (HT), including coronary artery disease, stroke, and, more in general, with increased risk of cardiovascular (CV) events. Hence, in this review we will analyse the relationship between the sleep disturbances associated with OSA and the altered function of the ANS, including CAs metabolism.

Keywords: Obstructive sleep apnoea (OSA); cardiovascular risk (CV risk); catecholamines (CAs); sympathetic nervous system (SNS).

Figure 1

Catecholamines metabolism (12). MAO, monoamine oxidase; AD, aldehyde dehydrogenase; AR, aldehyde reductase; COMT, catecol-O-methyl transferase.

Figure 2

Respiratory and autonomic changes during acute OSA. (A) Airflow trace; (B) thoracic and abdominal efforts traces. BP decreases during the initial part of the apnoea and rises when SpO₂ decreases at the end of the apnoeic event. When the ventilation resumes, HR and BP reach a peak (39). The increase in BP occurring during ventilation resumption may elicit a reduction in the ventilatory and sympathetic responses to chemoreflex stimulation by hypoxemia (40,41). Moreover during an apnoea, the lung inflation reflex may not occur, and this may contribute to an increase in ANS (42). In contrast, the reflex may be exacerbated during ventilation resumption, when ANS is abruptly inhibited; (C) oxygen saturation. Hypoxemia stimulates arterial chemoreceptors and causes an increase in efferent ANS (38). Hypercapnia may induce a higher ventilation, HR, cardiac output and BP (43); (D) heart rate trace. HR can slow down, increase or remain unchanged, depending on weather parasympathetic or sympathetic influences predominate (33). OSA, obstructive sleep apnoea; BP, blood pressure; HR, heart rate; ANS, autonomous nervous system.

Figure 3

Normal hypnogram (fragment)-frequency domain variables modifications during normal sleep. In normal subjects the transition from W to N1 is characterized by an increase of HF component (parasympathetic activation) and decrease of LF, which determines a decrease of LF/HF ratio. From N1 to N3, the stage of highest neural synchronization, an additional gradual decrease is observed in HR, with minimum values reached during N3, also called “deep sleep”. During REM stage LF values do not change significantly but the HF component decreases reaching the levels observed during the W; so the transition from NREM to REM is accompanied by an increase of HR (42). HF, high-frequency; LF, low-frequency; HR, heart rate; REM, rapid eye movement; NREM, non-rapid eye movement.