title: Excess prenatal corticosterone exposure results in albuminuria, sex-specific hypotension, and altered heart rate responses to restraint stress in aged adult mice.
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 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.
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia, Brisbane, Australia.
authors.forename: Lee
authors.initials: L
authors.lastname: O'Sullivan
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia, Brisbane, Australia.
authors.forename: James S M
authors.initials: JS
authors.lastname: Cuffe
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia, Brisbane, Australia.
authors.forename: Anselm
authors.initials: A
authors.lastname: Koning
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia, Brisbane, Australia.
authors.forename: Reetu R
authors.initials: RR
authors.lastname: Singh
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia, Brisbane, Australia.
authors.forename: Tamara M
authors.initials: TM
authors.lastname: Paravicini
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia, Brisbane, Australia k.moritz@uq.edu.au.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Moritz
mesh_terms: D000367:Age Factors; D000419:Albuminuria / Q000139:chemically induced* / Q000503:physiopathology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007022:Hypotension / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology; D012149:Restraint, Physical / Q000009:adverse effects* / Q000502:physiology; D012737:Sex Factors; D013315:Stress, Psychological / Q000150:complications* / Q000503:physiopathology; D013610:Tachycardia / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D003345:Corticosterone
keywords: developmental programming; glucocorticoid; hypotension; nephron deficit