Interleukin-2 protects against endothelial dysfunction induced by high glucose levels in rats

Vascul Pharmacol. 2006 Dec;45(6):374-82. doi: 10.1016/j.vph.2006.06.002. Epub 2006 Jun 12.

Abstract

Aims: Interleukin-2 (IL-2) can modulate cardiovascular functions, but the effect of IL-2 on vascular endothelial function in diabetes is not known. We hypothesized that IL-2 may attenuate endothelial dysfunction induced by high glucose or diabetes. So the aim of this study was to investigate the effect of IL-2 on endothelium-response of aortas incubated with high glucose or from diabetic rats and its underlying mechanism.

Methods: Acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR), sodium nitroprusside (SNP)-induced endothelium-independent relaxation (EIR), superoxide dismutase (SOD) and nitric oxide synthase (NOS) were measured in aortas isolated from non-diabetic rats and exposed to a high glucose concentration and from streptozotocin-induced diabetic rats.

Results: Incubation of aortic rings with high glucose (44 mM) for 4 h resulted in a significant inhibition of EDR, but had no effects on EIR. Co-incubation with IL-2 for 40 min prevented the inhibition of EDR caused by high glucose in a concentration-dependent manner. Similarly, high glucose decreased SOD and NOS activity in aortic tissue. IL-2 (1000 U/ml) significantly attenuated the decrease of SOD and NOS activity caused by high glucose. In addition, EDR declined along with the decrease of serum NO level in aortas from STZ-induced diabetic rats. Injection of IL-2 (5000 and 50,000 U kg(-1) d(-1), s.c.) for 5 weeks prevented the inhibition of EDR and the decrease of serum NO levels caused by diabetes.

Conclusions: IL-2 significantly ameliorated the endothelial dysfunction induced by hyperglycemia, in which the activation of the NO pathway and SOD may be involved.

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Aorta, Thoracic / drug effects*
  • Aorta, Thoracic / metabolism
  • Aorta, Thoracic / physiopathology
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / physiopathology*
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology
  • Glucose / pharmacology*
  • In Vitro Techniques
  • Interleukin-2 / pharmacology*
  • Male
  • Nitric Oxide / blood
  • Nitric Oxide Synthase / metabolism
  • Nitroprusside / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / metabolism
  • Time Factors
  • Vasodilation / drug effects*
  • Vasodilator Agents / pharmacology

Substances

  • Interleukin-2
  • Vasodilator Agents
  • Nitroprusside
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Superoxide Dismutase
  • Glucose
  • Acetylcholine