Endothelin-1 plasma levels are not elevated in patients with obstructive sleep apnoea

Abstract

Endothelin-1 (ET-1), a potent vasoconstrictor, is released mainly by vascular endothelial cells under the influence of hypoxia and other stimuli. ET-1 is related to endothelial dysfunction, as well as arterial and pulmonary hypertension, all of which are thought to be associated with obstructive sleep apnoea (OSA).This study evaluated venous plasma concentrations of ET-1 and noradrenaline and 24-h systemic blood pressure in 29 patients with OSA (age=56.9 1.6 yrs; body mass index=29.5 0.7 kg . m -2 (mean SEM)). Blood samples were taken in the morning, evening and during sleep. In the same way, the patients were assessed during a night of continuous positive airway pressure (CPAP) and after 13.9 1.4 months while still on CPAP. ET-1 levels were compared to those of control subjects, who were selected from in-and outpatients and were matched to patients for age, sex, presence of arterial hypertension and coronary artery disease.ET-1 plasma levels were not elevated in the patients compared to the controls (41.6 2.2 and 44.9 1.3 pg . mL -1 , respectively, p=0.20). The ET-1 concentration did not change significantly, neither during sleep nor in the first night on CPAP therapy, nor under long-term treatment with CPAP. ET-1 neither correlated to the severity of OSA nor to that of systemic hypertension.The results suggest that endothelin-1 does not play a crucial role in the pathophysiology of obstructive sleep apnoea. Endothelins are peptides of 21 amino acids that are produced in a wide variety of cells. Endothelin-1 (ET-1) was isolated from vascular endothelial cells [1], whereas endothelin-2 (ET-2) and endothelin-3 (ET-3) are mainly produced within the kidney and intestine. ET-1 is released under the influence of chemical or physical stimuli, such as hypoxia or shear stress, as well as various receptor operated mechanisms. It is the most potent endogenous vasoconstrictor yet identified and seems to be intimately involved in the pathogenesis of pulmonary hypertension [2,3]. Whether ET-1 production is increased in arterial hypertension remains controversial though [4]. Patients with obstructive sleep apnoea (OSA) exhibit repetitive nocturnal apnoeas and hypopnoeas which result in oxygen desaturations and consecutive arousals. OSA can be successfully treated with continuous positive airway pressure (CPAP). The disease can be associated with pulmonary hypertension even in the absence of daytime hypoxaemia or concomitant lung disease [5,6]. In epidemiological and animal studies an association between systemic hypertension and OSA, independent of obesity, age and sex, was found [7,8]. It is therefore tempting to speculate that in OSA plasma ET-1 levels are elevated due to nocturnal desaturations and give rise to pulmonary as well as arterial hypertension. To further elucidate this hypothesis the authors' studied the influence of CPAP treatment on ET-1 plasma concentration in patients with OSA. Methods Subjects and protocolTwenty-nine consecutive subjects of both sexes that were referred to the authors' sleep labor...

Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities

“…The endothelium also produces vasoconstrictor substances, such as endothelin and angiotensin II, and levels have been reported as increased in OSAS and to fall with effective CPAP therapy [323]. However, other reports did not find an increase of endothelin in OSAS [324]. The Sleep Heart Health Study has also reported evidence of vascular dysfunction among older participants, particularly arterial diameter [325], identifying OSAS as an independent risk factor for impaired flow-mediated vasodilation.…”

Increased Plasma Levels of Asymmetric Dimethylarginine and Soluble CD40 Ligand in Patients with Sleep Apnea

“…However, the potential role of the confounding factors mentioned above was not specifically considered. On the other hand, ET-1, a potent vasoconstrictor produced by endothelial cells, has also been implicated in the pathogenesis of endothelial dysfunction and CV disease [27, 28], but studies in patients with OSAS have yielded conflicting results [29, 30]. …”

Role of Endothelin in Intermittent Hypoxia-Induced Hypertension

“…Furthermore, this same study found that correction of sleep apnea reduced plasma endothelin to control levels. 8,9 However, Grimpen and coworkers 10 compared patients with obstructive sleep apnea with age-and weight-matched control subjects and found no differences in plasma levels of endothelin and no change in plasma endothelin after correction of the sleep apnea. Therefore, clinical studies do not provide a clear indication of the role of endothelin in sleep apnea-induced hypertension.…”