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Poster Abstract PresentationsSession Title: Developmental Programming/Gender Differences/Pregnancy

Abstract P169: Antenatal Betamethasone Attenuates the Angiotensin-(1-7)/Nitric Oxide Axis in Adult Male but not Female Renal Proximal Tubule Cells

Yixin Su, Victor M Pulgar, Jianli Bi, Mark Chappell, James C Rose
Hypertension. 2015;66:AP169
Yixin Su
Wake Forest Sch of Medicine, Winston Salem, NC
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Victor M Pulgar
Wake Forest Sch of Medicine, Winston Salem, NC
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Jianli Bi
Wake Forest Sch of Medicine, Winston Salem, NC
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Mark Chappell
Wake Forest Sch of Medicine, Winston Salem, NC
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James C Rose
Wake Forest Sch of Medicine, Winston Salem, NC
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Abstract

Our studies have revealed a sex-specific effect of fetal programming on sodium (Na+) excretion in adult sheep whereby the males exhibit reduced Na+ excretion and an attenuated natriuretic response to Ang-(1-7) as compared to the females. We hypothesize that the renal proximal tubules are a key target for the early programming effects of glucocorticoids exposure to regulate Na+ handling in the adult males. Therefore, we isolated and cultured cortical proximal tubule cells (RPTC) from adult male and female sheep antenatally exposed to betamethasone (Beta) or vehicle. Na+ uptake and nitric oxide (NO) were assessed with Sodium Green and DAF fluorescence prior to and following a low dose of Ang-(1-7) (1x10-11 M) in isolated RPTC from sheep at ~1.5 years of age. Data are expressed as % of basal uptake or area under the curve (AUC) for Na+ or % of control for NO. Male Beta RPTC exhibit greater Na+ uptake than male vehicle cells (427±32%, n=13, vs. 315±28%, n=14, p<0.05; however, Beta had no effect on Na+ uptake in the female cells (242±18%, n=9, vs. 250±15%, n=10, p>0.05). Ang-(1-7) inhibited Na+ uptake in RPTC from vehicle male (255±40%) and from both vehicle (191±14%) and Beta (209±11%) females (Figure 1B), but failed to attenuate Na+ uptake in Beta male cells (Figure 1A). Beta exposure also abolished NO stimulation by Ang-(1-7) in male but not female RPTC (Figure 1C). We conclude that an Ang-(1-7)-NO-dependent pathway contributes to the sex-dependent consequences of programming on Na+ regulation in the proximal tubules of the kidney. Moreover, the RPTC retain both the sex and Beta-induced phenotype of the adult and may reflect an appropriate cell model of fetal programming.


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  • cardiovascular developement
  • Hypertension, renal
  • Renal function
  • Author Disclosures: Y. Su: None. V.M. Pulgar: None. J. Bi: None. M. Chappell: None. J.C. Rose: None.

  • © 2015 by American Heart Association, Inc.
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Hypertension
September 2015, Volume 66, Issue Suppl 1
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    Abstract P169: Antenatal Betamethasone Attenuates the Angiotensin-(1-7)/Nitric Oxide Axis in Adult Male but not Female Renal Proximal Tubule Cells
    Yixin Su, Victor M Pulgar, Jianli Bi, Mark Chappell and James C Rose
    Hypertension. 2015;66:AP169, originally published November 3, 2015

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    Abstract P169: Antenatal Betamethasone Attenuates the Angiotensin-(1-7)/Nitric Oxide Axis in Adult Male but not Female Renal Proximal Tubule Cells
    Yixin Su, Victor M Pulgar, Jianli Bi, Mark Chappell and James C Rose
    Hypertension. 2015;66:AP169, originally published November 3, 2015
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