Insulin resistance impairs endothelial function but not adrenergic reactivity or vascular structure in fructose-fed rats

Olga P. Romanko, M. Irfan Ali, James D. Mintz, David W. Stepp

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Obesity and diabetes are major risk factors for the development of vascular disease in the lower limbs. Previous studies have demonstrated reduced nitric oxide (NO)-mediated vasodilation, increased adrenergic constriction, and inward, atrophic remodeling in the limb circulation of obese Zucker rats, but the component of the "metabolic syndrome" driving these changes is unclear. Because insulin resistance precedes the state of frank diabetes, the current study hypothesized that insulin resistance independent of obesity induced by fructose feeding would impair microvascular function in the skeletal muscle circulation in lean Zucker rats (LZR). A 66% fructose diet impaired glucose tolerance and induced moderate insulin resistance with no changes in whole-body hemodynamics of anesthetized rats (FF-LZR), compared to control LZR. NO-mediated vasodilation of isolated gracilis arteries, assessed in vitro with acetylcholine and sodium nitroprusside, was reduced ∼20% in FF-LZR vs. LZR. NO-independent cGMP-mediated vasodilation was unimpaired. Pretreatment of isolated vessels with the superoxide scavenger, tempol, improved responses to both vasodilators. Reactivity to adrenergic stimulation was unaltered in FF-LZR vs. LZR, although constriction to endothelin was increased. Structural and passive mechanical characteristics of isolated gracilis arteries were similar in both LZR and FF-LZR. Taken together, these findings indicate that moderate insulin resistance is sufficient to impair endothelial function in an oxidant-dependent manner in the rat hindlimb circulation. Other aspects of skeletal muscle vascular function documented in obese models, specifically adrenergic tone and inward remodeling, must reflect either severe insulin resistance or other aspects of obesity. The factors accounting for nonendothelial vasculopathies remain unknown.

Original languageEnglish (US)
Pages (from-to)414-423
Number of pages10
Issue number5
StatePublished - 2009


  • Adrenergic
  • Microcirculation
  • Nitric oxide
  • Super oxide

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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