CALL FOR PAPERS Developmental Origins of Health and Disease Excess prenatal corticosterone exposure results in albuminuria, sex-specific hypotension, and altered heart rate responses to restraint stress in aged adult mice

O’Sullivan L, Cuffe JS, Koning A, Singh RR, Paravicini TM, Moritz KM. Excess prenatal corticosterone exposure results in albuminuria, sexspecific hypotension, and altered heart rate responses to restraint stress in aged adult mice. Am J Physiol Renal Physiol 308: F1065–F1073, 2015. First published February 25, 2015; doi:10.1152/ajprenal.00676.2014.—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 g·kg ·h ) 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.