Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice.

نویسندگان

  • Anna Csiszar
  • Nazar Labinskyy
  • Viviana Perez
  • Fabio A Recchia
  • Andrej Podlutsky
  • Partha Mukhopadhyay
  • Gyorgy Losonczy
  • Pal Pacher
  • Steven N Austad
  • Andrzej Bartke
  • Zoltan Ungvari
چکیده

Hypopituitary Ames dwarf mice have low circulating growth hormone (GH)/IGF-I levels, and they have extended longevity and exhibit many symptoms of delayed aging. To elucidate the vascular consequences of Ames dwarfism we compared endothelial O2(-) and H2O2 production, mitochondrial reactive oxygen species (ROS) generation, expression of antioxidant enzymes, and nitric oxide (NO) production in aortas of Ames dwarf and wild-type control mice. In Ames dwarf aortas endothelial O2(-) and H2O2 production and ROS generation by mitochondria were enhanced compared with those in vessels of wild-type mice. In Ames dwarf aortas there was a less abundant expression of Mn-SOD, Cu,Zn-SOD, glutathione peroxidase (GPx)-1, and endothelial nitric oxide synthase (eNOS). NO production and acetylcholine-induced relaxation were also decreased in aortas of Ames dwarf mice. In cultured wild-type mouse aortas and in human coronary arterial endothelial cells treatment with GH and IGF significantly reduced cellular O2(-) and H2O2 production and ROS generation by mitochondria and upregulated expression of Mn-SOD, Cu,Zn-SOD, GPx-1, and eNOS. Thus GH and IGF-I promote antioxidant phenotypic changes in the endothelial cells, whereas Ames dwarfism leads to vascular oxidative stress.

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عنوان ژورنال:
  • American journal of physiology. Heart and circulatory physiology

دوره 295 5  شماره 

صفحات  -

تاریخ انتشار 2008