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

Background. Endothelium-dc pendent vasodilation is impaired in large condui t vessels in diabetes mellitus. Oxygen radicals contribute to the impaired endotholium-dependent vasodilation. We tested the hypothesis that stimulate d endothelium-dependent vasodilation is reduced in renal afferent arteriole s in diabetes and is caused bu an increase in vascular superoxide (O-2(-)). Methods. Renal afferent arterioles from normal and insulin-treated alloxan- diabetic rabbits were microdissected and microperfused in vitro for the stu dy of luminal diameter responses to acetylcholine (Ach; 10(-11) to 10(-6) m ol/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 norepinephine (NE)-preconstricted afferent arterioles of normal rabbits, Ach significantly (F < 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 married con trast, in NE-preconstricted arterioles of diabetic rabbits, Ach significant ly (P < 0.01) decreased luminal diameter by 41 <plus/minus> 11%. Pretreatme nt of diabetic afferent arterioles with the superoxide dismutase (SOD) mime tic tempol (10(-3) mol/L) restored a vasodilator response to Ach. In NE-pre constricted diabetic afferent arterioles treated with tempol, Ach significa ntlly (P < 0.001) increased luminal diameter by 25 <plus/minus> 6%. Conclusions. Ach-induced afferent arteriolar vasodilation is dependent on n itric oxide and is impaired in diabetes. O-2(-) contributes to the impaired Ach-induced vasodilation in renal afferent arterioles in diabetes.