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The effect of antenatal steroid exposure on sodium uptake in ovine renal proximal tubule cells (RPTC)
Author(s) -
Tang Lijun,
Bi Jianli,
Chappell Mark,
Figueroa Jorge,
Rose James C
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1029.12
Subject(s) - medicine , endocrinology , angiotensin ii , offspring , betamethasone , antagonist , receptor , receptor antagonist , chemistry , biology , pregnancy , genetics
Antenatal administration of clinically relevant doses of betamethasone (Beta) to pregnant sheep causes compromises of renal function in adult offspring. The present study was designed to examine whether antenatal betamethasone exposure at 80–81 days of gestation would impact sodium uptake by RPTC from adult ewes. RPTC were isolated from 1‐yr‐old female vehicle‐treated (N=7) and Beta‐treated (N=7) offspring and cultured for 10–14 days. The fluorescence dye sodium green was employed to determine cytoplasmic Na+ uptake. In the presence of the Na+/K+ ATPase inhibitor ouabain, Na+ uptake in RPTC was evaluated while exposed to different Na+ concentrations from 30 to 140 mmol/L. Prenatal steroid exposure did not alter basal Na+ uptake compared with vehicle treatment. Ang II (10 −11 M) increased Na+ uptake in both groups (F=6, P=.001 in vehicle; F=9, P<0.001 in Beta) and AT1 receptor antagonist‐candesartan abolished the AngII‐induced increase. There was no difference in responses to Ang II or Ang II with candesarten between two groups. In contrast, Ang‐(1–7) (10 −7 M) decreased cellular Na+ uptake in both groups (F=33 P<0.0001 in vehicle; F=53, P<0.0001 in Beta). However, Ang‐(1–7) plus D‐Ala (the Mas receptor antagonist) or PD (AT2 receptor antagonist) actually increased Na+ uptake and the increases were higher in Beta group than in vehicle group (D‐Ala: F=7, P<0.001; PD: F=14, P<0.001). These data suggest that prenatal betamethasone exposure converts the inhibitory effect of Ang‐(1–7) on Na+ uptake to a stimulatory action in the presence of blockade of the Mas or AT2 receptors. (Supported by HD47584 and HD17644)