Sex-specific effect of antenatal betamethasone exposure on renal oxidative stress induced by angiotensins in adult sheep

Jianli Bi, Stephen A. Contag, Kai Chen, Yixin Su, Jorge P. Figueroa, Mark C. Chappell, James C. Rose

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Prenatal glucocorticoid administration in clinically relevant doses reduces nephron number and renal function in adulthood and is associated with hypertension. Nephron loss in early life may predispose the kidney to other insults later but whether sex influences increases in renal susceptibility is unclear. Therefore, we determined, in male and female adult sheep, whether antenatal glucocorticoid (betamethasone) exposure increased 8-isoprostane (marker of oxidative stress) and protein excretion after acute nephron reduction and intrarenal infusions of angiotensin peptides. We also examined whether renal proximal tubule cells (PTCs) could contribute to alterations in 8-isoprostane excretion in a sex-specific fashion. In vivo, ANG II significantly increased 8-isoprostane excretion by 49% and protein excretion by 44% in male betamethasone- but not in female betamethasone- or vehicle-treated sheep. ANG-(1-7) decreased 8-isoprostane excretion but did not affect protein excretion in either group. In vitro, ANG II stimulated 8-isoprostane release from PTCs of male but not female betamethasone-treated sheep. Male betamethasone-exposed sheep had increased p47 phox abundance in the renal cortex while superoxide dismutase (SOD) activity was increased only in females. We conclude that antenatal glucocorticoid exposure enhances the susceptibility of the kidney to oxidative stress induced by ANG II in a sex-specific fashion and the renal proximal tubule is one target of the sex-specific effects of antenatal steroids. ANG-(1-7) may mitigate the impact of prenatal glucocorticoids on the kidney. P47 phox activation may be responsible for the increased oxidative stress and proteinuria in males. The protection from renal oxidative stress in females is associated with increased SOD activity.

Original languageEnglish (US)
Pages (from-to)F1013-F1022
JournalAmerican Journal of Physiology - Renal Physiology
Volume307
Issue number9
DOIs
StatePublished - Nov 1 2014
Externally publishedYes

Keywords

  • 8-isoprostane
  • Fetal programming
  • Intrarenal infusion
  • Kidney
  • Proteinuria

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