Antioxidants inhibit ATP-sensitive potassium channels in cerebral arterioles.
OBJECTIVE
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 source of hydroxyl radical in pathophysiological conditions and to clarify the mechanisms by which antioxidants modify vascular actions of oxidants.


METHODS
We investigated the effect of three antioxidants--dimethylsulfoxide (DMSO), salicylate, and L-cysteine--on the cerebral arteriolar dilation caused by topical application of hydrogen peroxide and peroxynitrite 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 effective 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 potassium channel openers, pinacidil and cromakalim. Their effect was specific because they did not affect dilation from adenosine or nitroprusside.


CONCLUSIONS
The findings show that antioxidants block ATP-sensitive potassium channels in cerebral arterioles. This appears to be the mechanism by which antioxidants inhibit the dilation from hydrogen peroxide and peroxynitrite and not through scavenging of a common intermediate, ie, hydroxyl radical. The differences between effectiveness in inhibiting 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.
Wei
E P
EP
Department of Medicine, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond 23298-0549, USA.
Kontos
H A
HA
Beckman
J S
JS
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001160:Arterioles / Q000187:drug effects*; D001921:Brain / Q000098:blood supply*; D002415:Cats; D003545:Cysteine / Q000627:therapeutic use; D004121:Dimethyl Sulfoxide / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000494:pharmacology; D017665:Hydroxyl Radical; D015221:Potassium Channels / Q000187:drug effects*; D012459:Salicylates / Q000627:therapeutic use; D020156:Salicylic Acid
D000975:Antioxidants; D016166:Free Radical Scavengers; D015221:Potassium Channels; D012459:Salicylates; D017665:Hydroxyl Radical; D000255:Adenosine Triphosphate; D003545:Cysteine; D020156:Salicylic Acid; D004121:Dimethyl Sulfoxide