Differential effects of clinical doses of antenatal betamethasone on nephron endowment and glomerular filtration rate in adult sheep.
Antenatal steroid administration is associated with alterations in fetal kidney development and hypertension. However, a causal relationship between nephron deficit and hypertension has not been established. In this study, we measured nephron number, renal function, and blood pressure in sheep exposed antenataly to betamethasone. Pregnant sheep were given 2 betamethasone doses (0.17 mg/kg) or vehicle at 80 and 81 days gestational age and allowed to deliver at term. Data were obtained from a fetal cohort and 2 adult cohorts and were analyzed by analysis of variance (ANOVA) and/or 2 sample t test. Antenatal betamethasone induced a 26% reduction in the number of nephrons in both males and females in the absence of intrauterine growth restriction and/or prematurity. Adult males presented a reduction in glomerular filtration rate (GFR; 132 +/- 12.7 vs 114 +/- 7.0 mL/min, P < .05). Betamethasone administration was also associated with an increase in arterial blood pressure of similar magnitude in male (mean arterial pressure [MAP] in mm Hg; 98 +/- 2.7 vs 105 +/- 2.4) and female (96 +/- 1.9 vs 105 +/- 2.4) adult sheep and the increase in blood pressure preceded the decrease in GFR in the males. Furthermore, we found no significant association between the magnitude of the decrease in nephron number and the magnitude of the increase in arterial blood pressure. Our data thus support the conclusion that exposure to glucocorticoids at a time of rapid kidney growth is associated with an elevation in blood pressure that does not appear related solely to the reduction in nephron number.
Zhang
Jie
J
Perinatal Research Laboratory, Department of Obstetrics and Gynecology, Center for Research in Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Massmann
G Angela
GA
Rose
James C
JC
Figueroa
Jorge P
JP
D000367:Age Factors; D000818:Animals; D001623:Betamethasone / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006977:Hypertension, Renal / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D007444:Inulin; D007677:Kidney Function Tests; D008297:Male; D009399:Nephrons / Q000002:abnormalities* / Q000473:pathology / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology* / Q000503:physiopathology; D012756:Sheep; D010130:p-Aminohippuric Acid
D005938:Glucocorticoids; D007444:Inulin; D001623:Betamethasone; D010130:p-Aminohippuric Acid