Carbamylated form of human erythropoietin normalizes cardiorespiratory disorders triggered by intermittent hypoxia mimicking sleep apnea syndrome
Autor
Andrade, David Cristóbal
Toledo, Camilo
Díaz, Hugo S.
Pereyra, Katherin V.
Schwarz, Karla G.
Díaz-Jara, Esteban
Melipillán, Claudia A.
Ríos-Gallardo, Angélica P.
Uribe-Ojeda, Atenea
Alcayaga, Julio
Quintanilla, Rodrigo A.
Iturriaga, R.
Resumen
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.
Colecciones
Ítems relacionados
Mostrando ítems relacionados por Título, autor o materia.
-
Article
Paraquat herbicide diminishes chemoreflex sensitivity, induces cardiac autonomic imbalance and impair cardiac function in rats (2021)
Pereyra, Katherin V.; Schwarz, Karla G.; Andrade, David Cristóbal; Toledo, Camilo; Ríos-Gallardo, Angélica P.; Díaz-Jara, Esteban; Bastías, Sussy S.; Ortiz, Fernando C.; Ortolani, Domiziana; del Río, Rodrigo R. (NLM (Medline), 2021-04-01)Paraquat (PQT) herbicide is widely used in agricultural practices despite being highly toxic to humans. It has been proposed that PQT exposure may promote cardiorespiratory impairment. However, the physiological mechanisms ... -
Article
Exercise training reduces brainstem oxidative stress and restores normal breathing function in heart failure (2021)
Díaz-Jara, Esteban; Díaz, Hugo S.; Ríos-Gallardo, Angélica P.; Ortolani, Domiziana; Andrade, David Cristóbal; Toledo, Camilo; Pereyra, Katherin V.; Schwarz, Karla G.; Ramirez, Gigliola; Ortiz, Fernando C.; ... (Elsevier Inc., 2021-08-20)Enhanced central chemoreflex drive and irregular breathing are both hallmarks in heart failure (HF) and closely related to disease progression. Central chemoreceptor neurons located within the retrotrapezoid nucleus (RTN) ... -
Article
Exercise intolerance in volume overload heart failure is associated with low carotid body mediated chemoreflex drive (2021)
Andrade, David Cristóbal; Díaz-Jara, Esteban; Toledo, Camilo; Schwarz, Karla G.; Pereyra, Katherin V.; Díaz, Hugo S.; Marcus, Noah J.; Ortiz, Fernando C.; Ríos-Gallardo, Angélica P.; Ortolani, Domiziana; ... (Nature Research, 2021-12)Mounting an appropriate ventilatory response to exercise is crucial to meeting metabolic demands, and abnormal ventilatory responses may contribute to exercise-intolerance (EX-inT) in heart failure (HF) patients. We sought ...