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 vasoconstr iction in subcutaneous arteries from patients with type II diabetes. M ethods: Small subcutaneous arteries (inner diameter = 90 to 180 mu m) from control subjects (n = 22) and patients with diabetes (n = 18) wer e dissected from skin biopsies obtained at surgery and mounted on a sp ecialized arteriograph that allowed for continuous measurement of lume n diameter under controlled pressure. The sensitivity to norepinephrin e was compared in arteries that were either intact, denuded of endothe lium, or intact and exposed to Nw-nitro-L-arginine (L-NNA), an inhibit or of nitric oxide synthesis. Stimulated release of nitric oxide by ac etylcholine and smooth muscle cell responses to sodium nitroprusside w ere also evaluated in diabetic and control arteries. Results: Sensitiv ity to norepinephrine was augmented in diabetic arteries and the amoun t 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 endotheli al removal and blockade of nitric oxide synthesis increased sensitivit y to norepinephrine in control arteries (EC(50 denuded) = 0.14 +/- 0.0 3 mu mol/L and EC(50 L-NNA) = 0.14 +/- 0.04 mu mol/L; p < 0.01) but fa iled to augment sensitivity in diabetic arteries (EC(50 denuded) = 0.1 7 +/- 0.05 mu mol/L and EC(50 L-NNA) = 0.15 +/- 0.04 mu mol/L; p > 0.0 5). Stimulated release of nitric oxide by acetylcholine was increased in the diabetic arteries: EC(50 control) = 0.04 +/- 0.01 mu mol/L vers us 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 mitiga tes adrenergic reactivity in control arteries, which is lacking in dia betic arteries and results in enhanced reactivity to norepinephrine; i ncreased sensitivity of diabetic arteries to acetylcholine, however, i ndicates a possible alteration at the receptor level.