Increased superoxide anion formation in endothelial cells during hyperglycemia: an adaptive response or initial step of vascular dysfunction?

Diabetes Res Clin Pract. 1999 Sep;45(2-3):153-60. doi: 10.1016/s0168-8227(99)00045-5.


In diabetes mellitus, the risk for cardiovascular complications and development of atherosclerosis is increased compared with healthy individuals. Recently evidence was provided that increased production of superoxide anions occurs in endothelial cells during hyperglycemia. In order to evaluate the potential impact of the enhanced formation of this oxygen radical for vascular cell dysfunction and its role in tissue adaptation, it is essential to assess the effect of superoxide anions on endothelial cell function. Here, we present new data and review our previous work on the effects of superoxide anions on endothelial vascular function, such as intracellular Ca2+ signal cascade, formation and bioactivity of nitric oxide. Based on the presented data we discuss superoxide anion production as a two faced phenomenon. In lower concentrations, superoxide anions are mediators of an endothelium adaptation to ensure endothelial vasomotion control. However, in higher concentrations superoxide anions disrupt endothelial-smooth muscle crosstalk resulting in vessel wall dysfunction and vascular wall dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Aorta
  • Arteries
  • Calcium / metabolism
  • Cells, Cultured
  • Diabetic Angiopathies / etiology
  • Diabetic Angiopathies / physiopathology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / physiology
  • Female
  • Glucose / pharmacology*
  • Hyperglycemia / metabolism*
  • Models, Cardiovascular
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / physiology
  • Nitric Oxide / metabolism
  • Signal Transduction
  • Superoxides / metabolism*
  • Swine
  • Uterus / blood supply
  • Xanthine / pharmacology
  • Xanthine Oxidase / pharmacology


  • Superoxides
  • Xanthine
  • Nitric Oxide
  • Xanthine Oxidase
  • Glucose
  • Calcium