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Antenatal Steroid Exposure is Associated with Reduced Urinary ACE2 Activity in Adolescents
Author(s) -
Gwathmey TanYa M.,
Shaltout Hossam A.,
Nixon Patricia A.,
Rose James C.,
Washburn Lisa K.,
Chappell Mark C.
Publication year - 2010
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.24.1_supplement.605.1
Subject(s) - urinary system , creatinine , medicine , endocrinology , betamethasone , offspring , urine , pregnancy , physiology , biology , genetics
The therapeutic use of antenatal administration of glucocorticoids is now common for women at risk of pre‐term delivery. However, both human and animal studies have reported that offspring of the treated mother exhibit increased mean arterial pressure (MAP) by adulthood. To evaluate a potential role for the renal renin angiotensin system (RAS) in humans, we assessed angiotensin (Ang) metabolism in urine collected from adolescents (14 years old) exposed antenatally to betamethasone (BMX; n=18) compared to that of non‐exposed individuals (CON; n=25). ACE activity, determined by the hydrolysis of radiolabeled 125 I‐Ang I to 125 I‐Ang II was not significantly different between groups (BMX: 0.71±0.10 vs. CON: 0.93±0.12 fmol/min/g creatinine). However, conversion of 125 I‐Ang II to 125 I‐Ang (1–7) by ACE2 was reduced by antenatal BMX exposure (BMX: 0.66±0.16 vs. CON: 1.09±0.17 fmol/min/g creatinine; P=0.04). MAP did not differ between groups at this age (BMX: 76±1 vs. CON: 75±1 mmHg). These data reveal that adolescents exposed to antenatal BMX treatment exhibit reduced urinary ACE2 activity in the absence of alterations in MAP. Moreover, the present study supports our findings in a sheep BMX model of fetal programming in which tubular and urinary ACE2 activity was reduced. We conclude that alterations in urinary (renal) ACE2 during adolescence may serve as a biomarker for the development of hypertension in adulthood.