Repository logo
 

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

Andrade, David C.
[1]; 
Toledo, Camilo
[1]; 
Diaz, Hugo S.
[1]; 
Pereyra, Katherin
[1]; 
Schwarz, Karla G.
[2]; 
Diaz-Jara, Esteban
[1]; 
Melipillan, Claudia
[2]; 
Rios-Gallardo, Angelica P.
[2]; 
Uribe-Ojeda, Atenea
[2]; 
Alcayaga, Julio
[3]; 
Quintanilla, Rodrigo A.
[4]; 
Iturriaga, Rodrigo
[1]; 
Richalet, Jean-Paul
[5]; 
Voituron, Nicolas
[5]; 
Del Rio, Rodrigo
[2]
  • 1
    Pontificia Universidad Catolica de Chile
  • 2
    Universidad de Magallanes  
  • 3
    Universidad de Chile
  • 4
    Universidad Autonoma de Chile
  • 5
    Institut National de la Sante et de la Recherche Medicale (Inserm)
DOI
Date Issued
2021-6
Type
Artículo
Journal
Journal of Hypertension
ISSN
0263-6352
1473-5598
Open Access
closed
Volume
39
Start page
1125
End page
1133
Links
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% O-2, 12/h, 8 h/day) for 28 days. cEPO (20 mu g/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.
Sugerencias y
Reporte de errores