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This Article Full Text Full Text (PDF) All Versions of this Article: 295/5/H1882    most recent 412.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Csiszar, A. Articles by Ungvari, Z. PubMed PubMed Citation Articles by Csiszar, A. Articles by Ungvari, Z.

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

¹Department of Physiology, New York Medical College, Valhalla, New York; ²Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, Texas; ³Sector of Medicine, Scuola Superiore Sant'Anna, Pisa, Italy; ⁴Section on Oxidative Stress Tissue Injury, Laboratory of Physiological Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; ⁵Department of Pulmonology, Semmelweis University, Budapest, Hungary; and ⁶Geriatrics Research, Departments of Internal Medicine and Physiology, Southern Illinois University School of Medicine, Springfield, Illinois

Submitted 18 April 2008 ; accepted in final form 14 August 2008

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.

senescence; vascular disease; atherosclerosis; Prop1^df/df mice