Endothelial function and adrenergic reactivity in human type-II diabetic resistance arteries

Purpose: This study was performed to examine the role of the vascular endothelium in modulating arterial reactivity to adrenergic vasoconstriction in subcutaneous arteries from patients with type II diabetes. Methods: Small subcutaneous arteries (inner diameter = 90 to 180 mu m) from control subjects (n = 22) and patients with diabetes (n = 18) were dissected from skin biopsies obtained at surgery and mounted on a specialized arteriograph that allowed for continuous measurement of lumen diameter under controlled pressure. The sensitivity to norepinephrine was compared in arteries that were either intact, denuded of endothelium, or intact and exposed to Nw-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide synthesis. Stimulated release of nitric oxide by acetylcholine and smooth muscle cell responses to sodium nitroprusside were also evaluated in diabetic and control arteries. Results: Sensitivity to norepinephrine was augmented in diabetic arteries and the amount of agonist necessary to contract the vessels 50% of maximum (EC(50)) decreased from 0.35 +/- 0.05 mu mol/L in the control arteries to 0.16 +/- 0.06 mu mol/L in the diabetic arteries (p < 0.05). Both endothelial removal and blockade of nitric oxide synthesis increased sensitivity to norepinephrine in control arteries (EC(50 denuded) = 0.14 +/- 0.03 mu mol/L and EC(50 L-NNA) = 0.14 +/- 0.04 mu mol/L; p < 0.01) but failed to augment sensitivity in diabetic arteries (EC(50 denuded) = 0.17 +/- 0.05 mu mol/L and EC(50 L-NNA) = 0.15 +/- 0.04 mu mol/L; p > 0.05). Stimulated release of nitric oxide by acetylcholine was increased in the diabetic arteries: EC(50 control) = 0.04 +/- 0.01 mu mol/L versus EC(50 diabetic) = 0.009 +/- 0.001 mu mol/L (p < 0.05). Sensitivity of vascular smooth muscle to sodium nitroprusside was similar in both nondiabetic and diabetic arteries. Conclusions: The endothelium mitigates adrenergic reactivity in control arteries, which is lacking in diabetic arteries and results in enhanced reactivity to norepinephrine; increased sensitivity of diabetic arteries to acetylcholine, however, indicates a possible alteration at the receptor level.