title: Obesity impairs vascular relaxation in human subjects: hyperglycemia exaggerates adrenergic vasoconstriction arterial dysfunction in obesity and diabetes.
abstract: OBJECTIVE
  Arterial dysfunction occurs in obesity and diabetes. However, there is uncertainty about the relative contribution of endothelial dysfunction, smooth muscle dysfunction, or adrenergic hyperresponsiveness.
  
  
  RESULTS
  We examined forearm resistance vessel responses to intra-arterial vasoactive agents in matched subjects on no antihyperglycemic medications classified as (1) Type 2 diabetes, (2) impaired fasting glucose (IFG), (3) obese, and (4) nonobese. Responses to both acetylcholine and nitroprusside were impaired in obese, IFG, and diabetic subjects compared to nonobese. However, diabetic and IFG subjects had no further impairment than normoglycemic obese subjects. Gender-specific data revealed that obese, IFG, and diabetic males compared to nonobese males demonstrated impaired responses to nitroprusside. However, among females, obese, IFG, and diabetic subjects demonstrated impaired acetylcholine-mediated responses. Multivariate analyses revealed that gender and adiposity, but not glycemia, were strongly related to acetylcholine and nitroprusside responses. Vasoconstriction to norepinephrine was greater in subjects with diabetes and IFG compared to nondiabetic obese controls.
  
  
  CONCLUSIONS
  Microvascular vasodilator function is impaired in obesity, with little further impairment in IFG and Type 2 diabetes. Females appear more sensitive to the deleterious effect of obesity on endothelium-mediated resistance vessel function, and males to smooth muscle-mediated function. There is a specific increase in adrenergic vasoconstrictor responses in IFG and Type 2 diabetes independent of obesity.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Iowa City Veterans Affairs Medical Center and the University of Iowa, Iowa City, IA 52242, USA. william-sivitz@uiowa.edu
authors.forename: William I
authors.initials: WI
authors.lastname: Sivitz
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Wayson
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Bayless
authors.forename: Christine A
authors.initials: CA
authors.lastname: Sinkey
authors.forename: William G
authors.initials: WG
authors.lastname: Haynes
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology; D001783:Blood Flow Velocity; D015992:Body Mass Index; D048909:Diabetes Complications / Q000503:physiopathology*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009765:Obesity / Q000150:complications* / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology*; D014664:Vasodilation; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009638:Norepinephrine