The Effect of Superoxide Anion on Autoregulation of Cerebral Blood Flow

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; 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). CONCLUSIONS: These results suggest that O2*- increases basal CBF and impairs autoregulation of CBF, likely through the activation of KCa channels in cerebral VSMCs.