The SOD mimetic tempol restores vasodilation in afferent arterioles of experimental diabetes.
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.
Schnackenberg
C G
CG
Division of Nephrology and Hypertension, Georgetown University Medical Center, Washington, DC, USA. christine_g_schnackenberg@sbphrd.com
Wilcox
C S
CS
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply; D008297:Male; D011817:Rabbits; D012079:Renal Circulation / Q000187:drug effects*; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D013113:Spin Labels; D013482:Superoxide Dismutase; D000109:Acetylcholine; C001803:tempol