Carbamylated form of human erythropoietin normalizes cardiorespiratory disorders triggered by intermittent hypoxia mimicking sleep apnea syndrome.

Autor:	Andrade DC; Laboratory of Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago.; Centro de Fisiología y Medicina de Altura, Facultad de Ciencias de la Salud, Universidad de Antofagasta, Antofagasta., Toledo C; Laboratory of Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago.; Centro de Envejecimiento y Regeneración (CARE), Pontificia Universidad Católica de Chile, Santiago., Diaz HS; Laboratory of Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago., Pereyra KV; Laboratory of Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago., Schwarz KG; Laboratory of Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago.; Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas., Díaz-Jara E; Laboratory of Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago., Melipillan C; Laboratory of Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago.; Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas., Rios-Gallardo AP; Laboratory of Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago.; Centro de Envejecimiento y Regeneración (CARE), Pontificia Universidad Católica de Chile, Santiago.; Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas., Uribe-Ojeda A; Laboratory of Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago.; Centro de Envejecimiento y Regeneración (CARE), Pontificia Universidad Católica de Chile, Santiago.; Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas., Alcayaga J; Laboratorio de Fisiología Celular, Facultad de Ciencias, Universidad de Chile., Quintanilla RA; Institute of Biomedical Sciences, Universidad Autónoma de Chile., Iturriaga R; Laboratorio de Neurobiología, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago, Chile., Richalet JP; Laboratoire Hypoxie and Poumon - UMR INSERM U1272, Université Sorbonne Paris Nord., Voituron N; Laboratoire Hypoxie and Poumon - UMR INSERM U1272, Université Sorbonne Paris Nord.; Département STAPS, Université Sorbonne Paris Nord, Bobigny, France., Del Rio R; Laboratory of Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago.; Centro de Envejecimiento y Regeneración (CARE), Pontificia Universidad Católica de Chile, Santiago.; Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas.
Jazyk:	angličtina
Zdroj:	Journal of hypertension [J Hypertens] 2021 Jun 01; Vol. 39 (6), pp. 1125-1133.
DOI:	10.1097/HJH.0000000000002756
Abstrakt:	Background and Objective: Chronic intermittent hypoxia (CIH), one of the main features of obstructive sleep apnea (OSA), enhances carotid body-mediated chemoreflex and induces hypertension and breathing disorders. The carbamylated form of erythropoietin (cEpo) may have beneficial effects as it retains its antioxidant/anti-inflammatory and neuroprotective profile without increasing red blood cells number. However, no studies have evaluated the potential therapeutic effect of cEpo on CIH-related cardiorespiratory disorders. We aimed to determine whether cEpo normalized the CIH-enhanced carotid body ventilatory chemoreflex, the hypertension and ventilatory disorders in rats. Methods: Male Sprague-Dawley rats (250 g) were exposed to CIH (5% O2, 12/h, 8 h/day) for 28 days. cEPO (20 μg/kg, i.p) was administrated from day 21 every other day for one more week. Cardiovascular and respiratory function were assessed in freely moving animals. Results: Twenty-one days of CIH increased carotid body-mediated chemoreflex responses as evidenced by a significant increase in the hypoxic ventilatory response (FiO2 10%) and triggered irregular eupneic breathing, active expiration, and produced hypertension. cEpo treatment significantly reduced the carotid body--chemoreflex responses, normalizes breathing patterns and the hypertension in CIH. In addition, cEpo treatment effectively normalized carotid body chemosensory responses evoked by acute hypoxic stimulation in CIH rats. Conclusion: Present results strongly support beneficial cardiorespiratory therapeutic effects of cEpo during CIH exposure. (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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