The Effect of Superoxide Anion on Autoregulation of Cerebral Blood Flow

Abstract

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. CBF was monitored with laser Doppler flowmetry during increases in blood pressure. 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; DeltaCBF/DeltaMAP) 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 KCa channels in cerebral vascular smooth muscle cells (VSMCs; n=8). These results suggest that O2*- increases basal CBF and impairs autoregulation of CBF, likely through the activation of KCa channels in cerebral VSMCs.