Published Online
on November 17, 2005

A more recent version of this article appeared on December 1, 2005

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Submitted on May 10, 2005
Revised on August 17, 2005
Accepted on August 18, 2005

The Effect of Superoxide Anion on Autoregulation of Cerebral Blood Flow

Drazen Zagorac MD; Ken Yamaura MD; Cindy Zhang MD, PhD; Richard J. Roman PhD; and David R. Harder PhD^*

From the Cardiovascular Research Center (D.Z., K.Y., C.Z., R.J.R., D.R.H.) Department of Physiology, Medical College of Wisconsin; and Clement Zablocki VA Medical Center (D.R.H.), Milwaukee, Wis.

^* To whom correspondence should be addressed. E-mail: dharder{at}mcw.edu.

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; CBF/MAP) 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 O₂·^- to impair autoregulation of CBF (AI, 0.65±0.07 and 0.72±0.05 respectively; n=6). O₂·^- also increased the activity of K_Ca channels in cerebral vascular smooth muscle cells (VSMCs; n=8).

Conclusion--These results suggest that O₂·^- increases basal CBF and impairs autoregulation of CBF, likely through the activation of K_Ca channels in cerebral VSMCs.

Key words: free radicals • cerebral blood flow

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