Gender differences in the effects of antenatal betamethasone exposure on renal function in adult sheep.
Exposure to clinically relevant doses of glucocorticoids during fetal life increases blood pressure in adult male and female sheep. The purpose of this study was to evaluate the effects of prenatal exposure to betamethasone at 80-81 days of gestation on renal function in ewes and rams at 1.5 yr of age. In prenatal betamethasone-exposed males, compared with the vehicle-exposed animals, basal glomerular filtration rate (GFR) (1.93 +/- 0.08 vs. 2.27 +/- 0.10 ml.min(-1).kg body wt(-1)) and the ability to excrete an acute Na+ load (37.1 +/- 4.4 vs. 53.7 +/- 9.7%) were reduced. (P < 0.03 and P = 0.03, respectively). In contrast, prenatal betamethasone exposure had no effect on basal GFR, Na+ excretion, or the percentage of the Na+ load excreted during the experiment in females. Systemic infusions of ANG-(1-7) at 9 ng.min(-1).kg(-1) for 2 h had minimal effects on basal GFR, renal plasma flow, and Na+ excretion in males but increased Na+ excretion in females. However, the percentage of Na+ load excreted during ANG-(1-7) infusion did not change in prenatal betamethasone-exposed females (113.1 +/- 14.2 vs. 98.1 +/- 12.2%) compared with the significant increase in vehicle females (139.2 +/- 22.3 vs. 92.2 +/- 7.5%) (P = 0.01). The data indicate that antenatal betamethasone exposure produces gender-specific alternations in renal function and thus suggest that different mechanisms underlie the antenatal steroid-induced elevations in blood pressure in male and female offspring.
Tang
Lijun
L
Department of Obstetrics and Gynecology and Center of Research for Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. ltang@wfubmc.edu
Carey
Luke C
LC
Bi
Jianli
J
Valego
Nancy
N
Sun
Xiurong
X
Deibel
Philip
P
Perrott
James
J
Figueroa
Jorge P
JP
Chappell
Mark C
MC
Rose
James C
JC
D000367:Age Factors; D000375:Aging; D000803:Angiotensin I / Q000008:administration & dosage; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D001623:Betamethasone / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000652:urine; D005260:Female; D005865:Gestational Age; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D010446:Peptide Fragments / Q000008:administration & dosage; D011188:Potassium / Q000097:blood / Q000652:urine; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011507:Proteinuria / Q000139:chemically induced / Q000503:physiopathology; D017596:Renal Plasma Flow, Effective / Q000187:drug effects; D012737:Sex Factors; D012756:Sheep; D012964:Sodium / Q000097:blood / Q000652:urine
D000893:Anti-Inflammatory Agents; D010446:Peptide Fragments; D000803:Angiotensin I; D001623:Betamethasone; D012964:Sodium; D003404:Creatinine; C118790:angiotensin I (1-7); D011188:Potassium