Altered insulin-mediated and insulin-like growth factor-1-mediated vasorelaxation in aortas of obese Zucker rats

Int J Obes (Lond). 2007 Jan;31(1):72-7. doi: 10.1038/sj.ijo.0803364. Epub 2006 May 9.


Objective: Insulin and insulin-like growth factor-1 (IGF-1) have vasorelaxant effects in vivo, which is dependent on nitric oxide (NO) production. The aim of this study was to investigate the vasorelaxant responses mediated by insulin and/or IGF-1 in aortas of obese Zucker rats.

Methods: The thoracic aortas of eight lean and eight obese Zucker rats (6 months old) were isolated for vasorelaxation analysis. Insulin-induced and IGF-1-induced vasorelaxant responses were evaluated by the isometric tension of aortic rings in the organ bathes. The roles of phosphatidylinositol 3-kinase (PI3K) and nitric oxide synthase (NOS) in vasorelaxant responses were examined by treating selective inhibitors, such as wortmannin (an inhibitor of PI3K) and N (omega)-nitro-L-arginine methyl ester (L-NAME, a NOS inhibitor). In addition, the vascular responses to sodium nitroprusside (SNP), a direct vasodilator of vascular smooth muscle, were examined.

Results: The insulin-induced vasorelaxation in aortas of obese rats was significantly decreased, whereas the IGF-1-induced vasorelaxation was significantly increased, compared with that in lean rats. After the pre-administration of wortmannin or L-NAME, the altered insulin-induced or IGF-1-induced vasorelaxation was abolished. There was no significant difference in the SNP-induced vasorelaxation between lean and obese rats.

Conclusion: Our findings suggested that the decreased insulin-mediated vasorelaxation in obese rats appeared to be counteracted by the increased IGF-1-mediated vasorelaxation. Furthermore, the NO-dependent pathway was involved in the altered vasorelaxant responses. However, the SNP-induced vasorelaxation was not changed in obese rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / physiopathology
  • Enzyme Inhibitors / pharmacology
  • Insulin / pharmacology*
  • Insulin Antagonists / pharmacology
  • Insulin-Like Growth Factor I / pharmacology*
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / physiology
  • Nitroprusside / pharmacology
  • Obesity / physiopathology*
  • Phosphatidylinositol 3-Kinases / physiology
  • Phosphoinositide-3 Kinase Inhibitors
  • Rats
  • Rats, Zucker
  • Vasodilation / drug effects*
  • Vasodilator Agents / pharmacology*
  • Wortmannin


  • Androstadienes
  • Enzyme Inhibitors
  • Insulin
  • Insulin Antagonists
  • Phosphoinositide-3 Kinase Inhibitors
  • Vasodilator Agents
  • Nitroprusside
  • Insulin-Like Growth Factor I
  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester
  • Wortmannin