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

Presented at the Joint Meeting of the Society of Vascular Surgery and the International Society for Cardiovascular Surgery, North American Chapter, New Orleans, La., June 11-14, 1995.
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Abstract

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 μm) 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 Nω-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 (EC50) decreased from 0.35 ± 0.05 μmol/L in the control arteries to 0.16 ± 0.06 μmol/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 5 0 denuded = 0.14 ± 0.03 μmol/L and EC 5 0 L-NNA = 0.14 ± 0.04 μmol/L; p < 0.01) but failed to augment sensitivity in diabetic arteries (EC 5 0 denuded = 0.17 ± 0.05 μmol/L and EC 5 0 L-NNA = 0.15 ± 0.04 μmol/L; p > 0.05). Stimulated release of nitric oxide by acetylcholine was increased in the diabetic arteries: EC 5 0 control = 0.04 ± 0.01 μmol/L versus EC 5 0 diabetic = 0.009 ± 0.001 μmol/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. (J Vasc Surg 1996;23:940-9.)

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From the Department of Surgery, Division of Vascular Surgery, Oregon Health Sciences University, Portland.

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0741-5214/96/$5.00 + 0

Reprint requests: Marilyn J. Cipolla, MS, Division of Vascular Surgery; OP-11, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Rd., Portland, OR 97201.

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