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Vasoprotective effects of lifespan‐extending peripubertal GH replacement in Lewis dwarf rats
Author(s) -
Ungvari Zoltan,
Guatam Tripti,
Henthorn Jim,
Pinto John,
Yan Han,
Mitschelen Matthew,
Farley Julie,
Sonntag W.E.,
Csiszar Anna
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1093.11
Subject(s) - vasoprotective , endocrinology , medicine , biology , nitric oxide
In humans growth hormone deficiency (GHD) and low circulating levels of IGF‐1 significantly increase the risk for cerebrovascular disease. Genetic GH/IGF‐1‐deficiency in Lewis dwarf rats (DW) significantly increases the incidence of late‐life strokes, similar to the effects of GHD in elderly humans. Peripubertal treatment of DW rats with GH delays the occurrence of late‐life stroke, which results in a significant extension of lifespan. The present study was designed to characterize the vascular effects of lifespan‐extending peripubertal GH replacement in DW rats. We found peripubertal GHD in DW rats increases vascular oxidative stress, which is prevented by GH replacement. Peripubertal GHD did not alter vascular expression and activity of SOD and catalase. In contrast, cerebrovascular expression of Gpx‐1 was significantly decreased in DW vessels and this effect was reversed by GH treatment. Peripubertal GHD significantly decreases expression of the Nrf2 target genes NQO1 and GCLC in the cerebral arteries, whereas it does not affect expression and activity of eNOS and vascular expression of IGF‐1, IGF binding proteins and inflammatory markers. In conclusion, peripubertal GH/IGF‐1 deficiency confers pro‐oxidative cellular effects, which likely promote an adverse functional and structural phenotype in vasculature and results in accelerated vascular impairments later in life. (Funding: ADA, AFAR, NIH).