title: Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice.
abstract: 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.
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Csiszar
authors.forename: Nazar
authors.initials: N
authors.lastname: Labinskyy
authors.forename: Viviana
authors.initials: V
authors.lastname: Perez
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Recchia
authors.forename: Andrej
authors.initials: A
authors.lastname: Podlutsky
authors.forename: Partha
authors.initials: P
authors.lastname: Mukhopadhyay
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Losonczy
authors.forename: Pal
authors.initials: P
authors.lastname: Pacher
authors.forename: Steven N
authors.initials: SN
authors.lastname: Austad
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bartke
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Ungvari