Free oxygen radicals decrease electrical resistance of microvascular endothelium in brain

Abstract

The effect of free oxygen radicals on the electrical resistance of brain venular endothelium was studied in anesthetized frogs. The technique allowed continuous recording of the electrical resistance of the vascular wall reflecting its ionic permeability. The oxygen radicals were generated by an enzymatic reaction between xanthine oxidase and hypoxanthine supplied to the surface of the exposed brain. Electrical resistance of the venular endothelium decreased within 1-2 s after the reaction was initiated. Hypoxanthine (1 mM) and xanthine oxidase at a concentration of 10, 25, 50, 100, and 250 mU ml-1 lowered resistance to 1.0, 0.9, 0.8, 0.5 and 0.2 X control value, respectively, within a 3 min period of administration. The effect induced by 25 and 50 mU ml-1 of xanthine oxidase was readily reversible, whereas that induced by the two highest concentrations was irreversible within the observation time. The response was totally blocked by allopurinol as well as by superoxide dismutase plus catalase. Pretreatment with methylprednisolone or BW755C (an inhibitor of cyclo- and lipoxygenase) did not inhibit the response, nor did removal of calcium or magnesium from the extracellular medium. Free oxygen radicals are powerful agents that rapidly induce dynamic changes in the electrical resistance of brain vessels, supporting the notion that they may be important mediators of vascular endothelial damage in the brain.