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

Lee O'Sullivan, James S M Cuffe, Anselm Koning, Reetu R Singh, Tamara M Paravicini, Karen M. Moritz

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27 Citations (Scopus)

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 mug.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 approximately 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.
Original languageEnglish
Pages (from-to)F1065-F1073
Number of pages9
JournalAmerican Journal of Physiology-Renal Physiology
Volume308
Issue number10
DOIs
Publication statusPublished - May 2015
Externally publishedYes

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