Relationship between the endothelial dysfunction and the expression of the β1-subunit of BK channels in a non-hypertensive sleep apnea group.

Candela Caballero-Eraso,Carmen Carmona Bernal,Ángeles Sánchez Armengol,Pablo Stiefel,Jose Luis López-Campos,Rafael Moreno Luna,Rocío Muñoz-Hernández,María Isabel Asensio Cruz,James Andrew Rowley

doi:10.1371/journal.pone.0217138

Abstract

Study objectivesVascular damage must be diagnosed early in patients with hypertension. In this regard, endothelial dysfunction (ED) is an early sign of vascular disease and a predictor of cardiovascular diseases. In obstructive sleep apnea (OSA), intermittent hypoxia triggers ED, but mechanisms are not clear. In this context, it has been described that BK channels regulates arterial tone and that chronic and intermittent hypoxia downregulates the expression of the BK channel β1-subunit facilitating vasoconstriction. Thus, we investigated the relationship among hypoxemia, ED, and mRNA expression of the β1-subunit in patients with severe OSA. We aimed to assess (1) ED in non-hypertensive patients with OSA using laser-Doppler flowmetry, (2) BK β1-subunit mRNA expression, and (3) the impact of continuous positive airway pressure (CPAP) treatment on ED and β1-subunit regulation.MethodsOSA patients underwent 24-hour blood pressure monitoring to exclude hypertension. Laser-Doppler flowmetry was performed to assess ED, and β1-subunit mRNA expression was evaluated using a blood test of peripheral blood leukocytes at baseline and after 3 months of CPAP treatment.ResultsIn normotensive patients with OSA, endothelial function correlated with the severity of OSA. CPAP improved endothelial function in normotensive OSA patients and the speed of the arterial response was significantly correlated with β1-subunit mRNA expression. β1-subunit mRNA expression at baseline correlated inversely with its change after CPAP.ConclusionsSleep apnea is related to ED in normotensive patients with OSA. CPAP therapy improves endothelial function and regulates β1-subunit mRNA expression.

Highlights

The European Society of Hypertension and European Society of Cardiology (ESH/ESC) guidelines emphasize that subclinical vascular organ damage must be identified at an early, asymptomatic stage, because subclinical organ damage constitutes an intermediate stage in the continuum of vascular diseases such as hypertension
In normotensive patients with obstructive sleep apnea (OSA), endothelial function correlated with the severity of OSA
continuous positive airway pressure (CPAP) improved endothelial function in normotensive OSA patients and the speed of the arterial response was significantly correlated with β1-subunit mRNA expression. β1-subunit mRNA expression at baseline correlated inversely with its change after CPAP

Summary

Introduction

The European Society of Hypertension and European Society of Cardiology (ESH/ESC) guidelines emphasize that subclinical vascular organ damage must be identified at an early, asymptomatic stage, because subclinical organ damage constitutes an intermediate stage in the continuum of vascular diseases such as hypertension. Several studies have reported that OSA patients present altered endothelial function and an increase in cardiovascular morbidity [8,9,10,11], and that treatment with continuous positive airway pressure (CPAP) might improve ED [6,12]. A meta-analysis published in 2017 showed that patients with OSA presented poor endothelial function, as indicated by flowmediated dilatation, and that this may contribute to atherosclerosis development [13]. It may be that repetitive airway collapse during sleep causes intermittent hypoxia, triggering free radical production and stimulating the activation of transcription factors that cause a cascade of pathophysiological mechanisms, including vasoconstriction, increased vascular permeability, an inflammatory and prothrombotic state, atherosclerosis, platelet aggregation, and thrombosis [14,15,16]

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