ANTIOXIDANTS INHIBIT ATP-SENSITIVE POTASSIUM CHANNELS IN CEREBRAL ARTERIOLES

Background and Purpose-Hydrogen peroxide and peroxynitrite are capable of generating hydroxyl radical and are commonly suspected as sources of this radical in tissues. It would be useful to distinguish the sour ce of hydroxyl radical in pathophysiological conditions and to clarify the mechanisms by which antioxidants modify vascular actions of oxida nts, Methods-We investigated the effect of three antioxidants-dimethyl sulfoxide (DMSO), salicylate, and L-cysteine-on the cerebral arteriola r dilation caused by topical application of hydrogen peroxide and pero xynitrite in anesthetized cats equipped with cranial windows. We also tested the effect of these antioxidants on the vasodilation caused by pinacidil and cromakalim, two known openers of ATP-sensitive potassium channels, Results-DMSO was more effective in inhibiting dilation from hydrogen peroxide, whereas salicylate and L-cysteine were more effect ive in inhibiting dilation from peroxynitrite, All three antioxidants inhibited dilation in concentrations that were remarkably low (<1 mmol /L). All three antioxidants inhibited vasodilation from two known pota ssium channel openers, pinacidil and cromakalim. Their effect was spec ific because they did not affect dilation from adenosine or nitropruss ide, Conclusions-The findings show that antioxidants block ATP-sensiti ve potassium channels in cerebral arterioles. This appears to be the m echanism by which antioxidants inhibit the dilation from hydrogen pero xide and peroxynitrite and not through scavenging of a common intermed iate, ie, hydroxyl radical, The differences between effectiveness in i nhibiting dilation from hydrogen peroxide and peroxynitrite by various antioxidants suggest that hydrogen peroxide and peroxynitrite act at two different sites, one in a water-soluble environment and the other in a lipid-soluble environment.