Abstract: Objective To investigate the role of oxidative stress in impaired intermediate-conductance Ca2 +-activated potassium
channels (IKCa)- and small-conductance Ca2 +-activated potassium channels (SKCa)-mediated relaxation in diabetic resistance
arteries. Methods Rat diabetic model was induced by a high fat and high glucose diet and streptozotocin (STZ) injection.
Endothelial function of mesenteric arteries was assessed with the use of wire myography. The expression levels of IKCa and SKCa
in cultured human umbilical vein endothelial cells (HUVECs) treated with H2O2 and/or antioxidant alpha lipoic acid (ALA)
were measured using Western blotting. Results IKCa- and SKCa-mediated vasodilatation in response to acetylcholine was
impaired in the third-order mesenteric arterioles of diabetic rats. In cultured HUVECs, H2O2 significantly decreased the protein
expression of IKCa and SKCa. ALA alleviated the impairment of both vasodilatation function of the mesenteric arterioles ex vivo
and enhanced the expression of IKCa and SKCa challenged with H2O2 in cultured HUVECs. Conclusion Our data demonstrated
for the first time that impaired IKCa- and SKCa-mediated vasodilatation in diabetes was induced, at least in part, by oxidative
stress via down-regulation of IKCa and SKCa channels.