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

Abstract

Study objectives: Vascular 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.

Methods: OSA 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.

Results: In 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.

Conclusions: Sleep apnea is related to ED in normotensive patients with OSA. CPAP therapy improves endothelial function and regulates β1-subunit mRNA expression.

Trial registration: ClinicalTrials.gov NCT01791270.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. There is a relationship between…
Fig 1. There is a relationship between the oximetric patterns of non-hypertensive OSA patients and their endothelial function.
AUC: Area under the curve (perfusion units). *p

Fig 2. There is a correlation between…

Fig 2. There is a correlation between β1-subunit mRNA expression at baseline and its change…

Fig 2. There is a correlation between β1-subunit mRNA expression at baseline and its change after 3 months of CPAP treatment.
Pre-CPAP β1 mRNA: β1-subunit mRNA expression at baseline, post-CPAP β1 mRNA / pre-CPAP β1 mRNA: ratio of β1-subunit mRNA expression after 3 months of CPAP treatment to that at baseline. p = 0.009.

Fig 3. The endothelial function in non-hypertensive…

Fig 3. The endothelial function in non-hypertensive OSA patients was significantly correlated with β1-subunit mRNA…

Fig 3. The endothelial function in non-hypertensive OSA patients was significantly correlated with β1-subunit mRNA expression.
T. recovery: time to recovery. T. Latency: time to latency time. T. Maximum: time to maximum flow. pre-CPAP β1 mRNA: β1-subunit mRNA expression at baseline. post-CPAP β1 mRNA: β1-subunit mRNA expression after 3 months of CPAP treatment. * p
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References
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This work was supported by two grants: 1) Instituto de Salud Carlos III, PI/0044/07, to Dr. P. Stiefel (P.S). http://www.isciii.es/ISCIII/es/contenidos/fd-investigacion/fd-financiacion/fd-convocatoriasayudas-accion-estrategica-salud/acceso-solicitud-ayudas.shtml. 2) Consejeria de Salud, Junta de Andalucía, P09-CTS-4971, to Dra. M.A Sánchez-Armengol (A.S.A). https://www.juntadeandalucia.es/temas/estudiar/becas/nacionales.html. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Fig 2. There is a correlation between…
Fig 2. There is a correlation between β1-subunit mRNA expression at baseline and its change after 3 months of CPAP treatment.
Pre-CPAP β1 mRNA: β1-subunit mRNA expression at baseline, post-CPAP β1 mRNA / pre-CPAP β1 mRNA: ratio of β1-subunit mRNA expression after 3 months of CPAP treatment to that at baseline. p = 0.009.
Fig 3. The endothelial function in non-hypertensive…
Fig 3. The endothelial function in non-hypertensive OSA patients was significantly correlated with β1-subunit mRNA expression.
T. recovery: time to recovery. T. Latency: time to latency time. T. Maximum: time to maximum flow. pre-CPAP β1 mRNA: β1-subunit mRNA expression at baseline. post-CPAP β1 mRNA: β1-subunit mRNA expression after 3 months of CPAP treatment. * p

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