Stress worsens endothelial function and ischemic stroke via glucocorticoids

Stroke. 2011 Nov;42(11):3258-64. doi: 10.1161/STROKEAHA.110.607705. Epub 2011 Sep 15.


Background and purpose: Chronic stress is associated with increased stroke risk. However, the underlying pathophysiological mechanisms are poorly understood. We examined the effects of chronic stress on endothelial function and ischemic brain injury in a mouse model.

Methods: 129/SV mice were treated with glucocorticoid receptor antagonist mifepristone (25 mg kg(-1)/d) or vehicle and exposed to 28 days of chronic stress consisting of exposure to rat, restraint stress, and tail suspension. Heart rate and blood pressure were continuously recorded by telemetry. Endothelial nitric oxide synthase mRNA and protein expression as well as superoxide production and lipid hydroperoxides were quantified. Endothelium-dependent vasorelaxation was measured in aortic rings. Ischemic lesion volume was quantified after 30 minutes filamentous middle cerebral artery occlusion and 72 hours reperfusion.

Results: Chronic stress caused a significant increase in heart rate, impaired endothelium-dependent vasorelaxation, increased superoxide production, and reduced aortic and brain endothelial nitric oxide synthase levels. Animals exposed to chronic stress showed major increases in ischemic lesion size. These deleterious effects of stress were completely reversed by treatment with mifepristone.

Conclusions: Chronic stress increases stroke vulnerability likely through endothelial dysfunction, which can be reversed by a glucocorticoid receptor antagonist.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / metabolism*
  • Brain Ischemia / pathology
  • Brain Ischemia / physiopathology*
  • Cerebrovascular Circulation / physiology
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology*
  • Endothelium, Vascular / physiopathology
  • Glucocorticoids / physiology*
  • Male
  • Mice
  • Mice, 129 Strain
  • Random Allocation
  • Rats
  • Stress, Psychological / metabolism*
  • Stress, Psychological / pathology
  • Stroke / metabolism*
  • Stroke / pathology
  • Stroke / physiopathology*
  • Superoxides / metabolism


  • Glucocorticoids
  • Superoxides