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

Abstract

Background: Endothelium-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(-)).

Methods: Renal 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).

Results: In norepinephrine (NE)-preconstricted afferent arterioles of normal rabbits, Ach significantly (P < 0.001) increased luminal diameter by 165 +/- 44%. The nitric oxide synthase inhibitor N(omega)-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%.

Conclusions: Ach-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.