The effect of superoxide anion on autoregulation of cerebral blood flow

Drazen Zagorac, Ken Yamaura, Cindy Zhang, Richard J. Roman, David R. Harder

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background and Purpose - Recent studies have suggested that autoregulation of cerebral blood flow (CBF) is impaired after traumatic and ischemic brain injury. Given that the levels of superoxide anion (O2 .-) are increased in these conditions, we postulate that O2 .- contributes to the impairment of CBF autoregulation. Methods - CBF was monitored with laser Doppler flowmetry during increases in blood pressure. Results - During the control period, CBF was well autoregulated after the increase in mean arterial pressure (MAP) from 98±3 to 140±6 mm Hg. The autoregulation index (AI; ΔCBF/ΔMAP) averaged 0.25±0.02 (n=6). O2 .- in the brain was then increased by subdural perfusion of xanthine/xanthine oxidase (different concentrations) and catalase. Low concentrations of O2 .- decreased basal CBF by 10±1.6% but had no effect on autoregulation (AI, 0.19±0.02; n=6). Higher concentrations of O2 .- (0.2 mmol/L xanthine and either 3 or 20 mU xanthine oxidase) increased basal CBF by 30±2% and 42±4%, respectively, and impaired autoregulation of CBF (AI, 0.55±0.03 and 0.76±0.02; n=6). Inclusion of superoxide dismutase in the O2 .--generating system restored autoregulation (AI, 0.28±0.05; n=6). Neither inhibition of NO synthase nor the addition of deferioxamine had any effect on the ability of higher concentrations of O 2 .- to impair autoregulation of CBF (AI, 0.65±0.07 and 0.72±0.05 respectively; n=6). O2 .- also increased the activity of KCa channels in cerebral vascular smooth muscle cells (VSMCs; n=8). Conclusion - These results suggest that O 2 .- increases basal CBF and impairs autoregulation of CBF, likely through the activation of KCa channels in cerebral VSMCs.

Original languageEnglish
Pages (from-to)2589-2594
Number of pages6
JournalStroke
Volume36
Issue number12
DOIs
Publication statusPublished - Dec 1 2005
Externally publishedYes

Fingerprint

Cerebrovascular Circulation
Superoxides
Homeostasis
Xanthine
Xanthine Oxidase
Arterial Pressure
Laser-Doppler Flowmetry
Vascular Smooth Muscle
Nitric Oxide Synthase
Catalase

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

The effect of superoxide anion on autoregulation of cerebral blood flow. / Zagorac, Drazen; Yamaura, Ken; Zhang, Cindy; Roman, Richard J.; Harder, David R.

In: Stroke, Vol. 36, No. 12, 01.12.2005, p. 2589-2594.

Research output: Contribution to journalArticle

Zagorac, Drazen ; Yamaura, Ken ; Zhang, Cindy ; Roman, Richard J. ; Harder, David R. / The effect of superoxide anion on autoregulation of cerebral blood flow. In: Stroke. 2005 ; Vol. 36, No. 12. pp. 2589-2594.
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T1 - The effect of superoxide anion on autoregulation of cerebral blood flow

AU - Zagorac, Drazen

AU - Yamaura, Ken

AU - Zhang, Cindy

AU - Roman, Richard J.

AU - Harder, David R.

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N2 - Background and Purpose - Recent studies have suggested that autoregulation of cerebral blood flow (CBF) is impaired after traumatic and ischemic brain injury. Given that the levels of superoxide anion (O2 .-) are increased in these conditions, we postulate that O2 .- contributes to the impairment of CBF autoregulation. Methods - CBF was monitored with laser Doppler flowmetry during increases in blood pressure. Results - During the control period, CBF was well autoregulated after the increase in mean arterial pressure (MAP) from 98±3 to 140±6 mm Hg. The autoregulation index (AI; ΔCBF/ΔMAP) averaged 0.25±0.02 (n=6). O2 .- in the brain was then increased by subdural perfusion of xanthine/xanthine oxidase (different concentrations) and catalase. Low concentrations of O2 .- decreased basal CBF by 10±1.6% but had no effect on autoregulation (AI, 0.19±0.02; n=6). Higher concentrations of O2 .- (0.2 mmol/L xanthine and either 3 or 20 mU xanthine oxidase) increased basal CBF by 30±2% and 42±4%, respectively, and impaired autoregulation of CBF (AI, 0.55±0.03 and 0.76±0.02; n=6). Inclusion of superoxide dismutase in the O2 .--generating system restored autoregulation (AI, 0.28±0.05; n=6). Neither inhibition of NO synthase nor the addition of deferioxamine had any effect on the ability of higher concentrations of O 2 .- to impair autoregulation of CBF (AI, 0.65±0.07 and 0.72±0.05 respectively; n=6). O2 .- also increased the activity of KCa channels in cerebral vascular smooth muscle cells (VSMCs; n=8). Conclusion - These results suggest that O 2 .- increases basal CBF and impairs autoregulation of CBF, likely through the activation of KCa channels in cerebral VSMCs.

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