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  • Excess prenatal corticosterone exposure results in albuminuria, sex-specific hypotension, and altered heart rate responses to restraint stress in aged adult mice

    Author(s)
    O'Sullivan, Lee
    Cuffe, James SM
    Koning, Anselm
    Singh, Reetu R
    Paravicini, Tamara M
    Moritz, Karen M
    Griffith University Author(s)
    Cuffe, James S.
    Year published
    2015
    Metadata
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    Abstract
    Exposure to excess glucocorticoids programs susceptibility to cardiovascular and renal dysfunction in later life although the mechanisms have not been clearly elucidated. We administered corticosterone (CORT; 33 μg·kg−1·h−1) to pregnant mice for 60 h from embryonic day (E) 12.5. Prenatal CORT resulted in postnatal growth restriction and reduced nephron endowment at postnatal day 30 in both male and female offspring. The reduction in nephron number was associated with increased expression of apoptotic markers in the kidney at E14.5. In offspring of both sexes at 12 mo of age, there were no differences in kidney weights, urine ...
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    Exposure to excess glucocorticoids programs susceptibility to cardiovascular and renal dysfunction in later life although the mechanisms have not been clearly elucidated. We administered corticosterone (CORT; 33 μg·kg−1·h−1) to pregnant mice for 60 h from embryonic day (E) 12.5. Prenatal CORT resulted in postnatal growth restriction and reduced nephron endowment at postnatal day 30 in both male and female offspring. The reduction in nephron number was associated with increased expression of apoptotic markers in the kidney at E14.5. In offspring of both sexes at 12 mo of age, there were no differences in kidney weights, urine output, or urinary sodium excretion; however, prenatal CORT exposure increased the urinary albumin/creatinine ratio and 24-h urinary albumin excretion. Surprisingly, at 12 mo male but not female offspring exposed to prenatal CORT were hypotensive, with mean arterial blood pressures ∼10 mmHg lower than untreated controls (P < 0.001). Finally, we examined how offspring responded to a renal or cardiovascular challenge (saline load or restraint stress). When given 0.9% NaCl as drinking water for 7 days, there were no differences in blood pressures or urinary parameters between groups. Restraint stress (15 min) caused a tachycardic response in all animals; however the increase in heart rate was not sustained in male offspring exposed to CORT (P < 0.01), suggesting that autonomic control of cardiovascular function may be altered. These data demonstrate that excess prenatal CORT impairs kidney development and increases the risk of cardiovascular dysfunction especially in males.
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    Journal Title
    American Journal of Physiology: Renal Physiology
    Volume
    308
    Issue
    10
    DOI
    https://doi.org/10.1152/ajprenal.00676.2014
    Subject
    Zoology
    Clinical sciences
    Clinical sciences not elsewhere classified
    Medical physiology
    Publication URI
    http://hdl.handle.net/10072/173679
    Collection
    • Journal articles

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