Tubuloglomerular feedback responses in offspring of dexamethasone-treated ewes

Anita J. Turner*, Russell D. Brown, Amanda E. Brandon, A. Erik G. Persson, Karen J. Gibson

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Via developmental programming, prenatal perturbations, such as exposure to glucocorticoids and maternal malnutrition alter kidney development and contribute to the development of hypertension. To examine the possibility that alterations in tubuloglomerular feedback (TGF) contribute to the development of hypertension in offspring following maternal dexamethasone treatment (Dex) in early gestation, studies were conducted in fetal sheep and lambs. Pregnant ewes were infused with dexamethasone (0.48 mg/h) at 26-28 days gestation. No differences were observed in mean arterial pressure, glomerular filtration rate. or electrolyte excretion rates between the Dex and Untreated fetuses or lambs. Gestational exposure to Dex markedly enhanced TGF sensitivity, as the turning point in Dex-treated fetuses was significantly lower (12.9 + 0.9 nl/min; P < 0.05) compared with Untreated fetuses (17.0 + 1.0 nl/min). This resetting of TGF sensitivity persisted after birth (P < 0.01). TGF reactivity did not differ between the groups in fetuses or lambs. In response to nitric oxide inhibition, TGF sensitivity increased (the turning point decreased) and reactivity increased in Untreated fetuses and lambs, but these effects were blunted in the Dex-treated fetuses and lambs. Our data suggest that an altered TGF response may be an underlying renal mechanism contributing to the development of hypertension in the Dex model of fetal programming. The lower tonic level of NO production in these dexamethasone-exposed offspring may contribute to the development of hypertension as adults.

Original languageEnglish
Pages (from-to)F864-F873
Number of pages10
JournalAmerican Journal of Physiology - Renal Physiology
Volume313
Issue number4
DOIs
Publication statusPublished - 1 Oct 2017

Keywords

  • tubuloglomerular feedback
  • fetal programming
  • dexamethasone

Fingerprint Dive into the research topics of 'Tubuloglomerular feedback responses in offspring of dexamethasone-treated ewes'. Together they form a unique fingerprint.

Cite this