title: Endothelial function and adrenergic reactivity in human type-II diabetic resistance arteries.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Surgery, Oregon Health Sciences University, Portland 97201, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Cipolla
authors.forename: C T
authors.initials: CT
authors.lastname: Harker
authors.forename: J M
authors.initials: JM
authors.lastname: Porter
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries / Q000503:physiopathology; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012867:Skin / Q000098:blood supply; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D011942:Receptors, Adrenergic, alpha; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D009638:Norepinephrine