The SOD mimetic tempol restores vasodilation in afferent arterioles of experimental diabetes

The SOD mimetic tempol restores vasodilation in afferent arterioles of experimental diabetes.BackgroundEndothelium-dependent vasodilation is impaired in large conduit vessels in diabetes mellitus. Oxygen radicals contribute to the impaired endothelium-dependent vasodilation. We tested the hypothesis that stimulated endothelium-dependent vasodilation is reduced in renal afferent arterioles in diabetes and is caused by an increase in vascular superoxide (O2-).MethodsRenal afferent arterioles from normal and insulin-treated alloxan-diabetic rabbits were microdissected and microperfused in vitro for the study of luminal diameter responses to acetylcholine (Ach; 10-11 to 10-6 mol/L). The blood glucose concentration of insulin-treated alloxan-diabetic rabbits was elevated fourfold compared with normal rabbits (319 ± 23 vs. 79 ± 6 mg/dL, P < 0.001).ResultsIn norepinephrine (NE)-preconstricted afferent arterioles of normal rabbits, Ach significantly (P < 0.001) increased luminal diameter by 165 ± 44%. The nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (10-4 mol/L) blocked this Ach-induced vasodilation. In marked contrast, in NE-preconstricted arterioles of diabetic rabbits, Ach significantly (P < 0.01) decreased luminal diameter by 41 ± 11%. Pretreatment of diabetic afferent arterioles with the superoxide dismutase (SOD) mimetic tempol (10-3 mol/L) restored a vasodilator response to Ach. In NE-preconstricted diabetic afferent arterioles treated with tempol, Ach significantly (P < 0.001) increased luminal diameter by 25 ± 6%.ConclusionsAch-induced afferent arteriolar vasodilation is dependent on nitric oxide and is impaired in diabetes. O2- contributes to the impaired Ach-induced vasodilation in renal afferent arterioles in diabetes