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

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 microns) 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 N omega-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 mumol/L in the control arteries to 0.16 +/- 0.06 mumol/L in the diabetic arteries (p < 0.05). Both endothelial removal and blockade of nitric oxide synthesis increased sensitivity to norepinephrine in control arteries (EC50 denuded = 0.14 +/- 0.03 mumol/L and EC50 L-NNA = 0.14 +/- 0.04 mumol/L; p < 0.01) but failed to augment sensitivity in diabetic arteries (EC50 denuded = 0.17 +/- 0.05 mumol/L and EC50 L-NNA = 0.15 +/- 0.04 mumol/L; p > 0.05). Stimulated release of nitric oxide by acetylcholine was increased in the diabetic arteries: EC50 control = 0.04 +/- 0.01 mumol/L versus EC50 diabetic = 0.009 +/- 0.001 mumol/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.

journal_name

J Vasc Surg

journal_title

Journal of vascular surgery

authors

Cipolla MJ,Harker CT,Porter JM

doi

10.1016/s0741-5214(96)70261-6

subject

Has Abstract

pub_date

1996-05-01 00:00:00

pages

940-9

issue

5

eissn

0741-5214

issn

1097-6809

pii

S0741-5214(96)70261-6

journal_volume

23

pub_type

杂志文章

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