Chronic intermittent hypoxia-induced vascular enlargement and VEGF upregulation in the rat carotid body is not prevented by antioxidant treatment

Am J Physiol Lung Cell Mol Physiol. 2011 Nov;301(5):L702-11. doi: 10.1152/ajplung.00128.2011. Epub 2011 Aug 5.


Chronic intermittent hypoxia (CIH), a characteristic of sleep obstructive apnea, enhances carotid body (CB) chemosensory responses to hypoxia, but its consequences on CB vascular area and VEGF expression are unknown. Accordingly, we studied the effect of CIH on CB volume, glomus cell numbers, blood vessel diameter and number, and VEGF immunoreactivity (VEGF-ir) in male Sprague-Dawley rats exposed to 5% O(2), 12 times/h for 8 h or sham condition for 21 days. We found that CIH did not modify the CB volume or the number of glomus cells but increased VEGF-ir and enlarged the vascular area by increasing the size of the blood vessels, whereas the number of the vessels was unchanged. Because oxidative stress plays an essential role in the CIH-induced carotid chemosensory potentiation, we tested whether antioxidant treatment with ascorbic acid may impede the vascular enlargement and the VEGF upregulation. Ascorbic acid, which prevents the CB chemosensory potentiation, failed to impede the vascular enlargement and the increased VEGF-ir. Thus present results suggest that the CB vascular enlargement induced by CIH is a direct effect of intermittent hypoxia and not secondary to the oxidative stress. Accordingly, the subsequent capillary changes may be secondary to the mechanisms involved in the neural chemosensory plasticity induced by intermittent hypoxia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Ascorbic Acid / pharmacology*
  • Carotid Body* / metabolism
  • Carotid Body* / pathology
  • Carotid Body* / physiopathology
  • Cell Count
  • Chemoreceptor Cells / cytology
  • Chemoreceptor Cells / drug effects
  • Chemoreceptor Cells / metabolism
  • Hypoxia / complications*
  • Hypoxia / drug therapy
  • Hypoxia / metabolism
  • Hypoxia / physiopathology
  • Immunohistochemistry
  • Male
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Sleep Apnea, Obstructive / complications
  • Sleep Apnea, Obstructive / drug therapy
  • Sleep Apnea, Obstructive / metabolism
  • Sleep Apnea, Obstructive / physiopathology
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / biosynthesis*


  • Antioxidants
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Ascorbic Acid