Antenatal betamethasone exposure alters renal responses to angiotensin-(1-7) in uninephrectomized adult male sheep

Jianli Bi, Stephen A. Contag, Luke C. Carey, Lijun Tang, Nancy K. Valego, Mark C. Chappell, James C. Rose

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Antenatal corticosteroid exposure reduces renal function and alters the intrarenal renin-angiotensin system to favor angiotensin activation of angiotensin type 1 receptor (AT1R) mediated responses in ovine offspring. This study aimed to assess whether antenatal steroid exposure would affect renal responses to the direct intrarenal infusion of angiotensin-(1-7) in rams and the angiotensin receptors involved in mediating responses to the peptide.Adult, uninephrectomized rams exposed to either betamethasone or vehicle before birth received intrarenal angiotensin-(1-7) infusions (1 ng/kg/min) alone or in combination with antagonists to angiotensin receptors for 3 h. Basal sodium excretion (UNa) was significantly lower and mean arterial pressure was significantly higher in betamethasone- compared to the vehicle-treated sheep. Angiotensin-(1-7) decreased UNa more in betamethasone- than in vehicle-treated sheep. Candesartan reversed the response to angiotensin-(1-7) but D-Ala7-angiotensin-(1-7) did not. Angiotensin-(1-7) infusion decreased effective renal plasma flow in both groups to a similar extent and the response was reversed by candesartan, but was not blocked by D-Ala7-angiotensin-(1-7). Glomerular filtration rate increased significantly in both groups after 3 h infusion of angiotensin-(1-7) plus candesartan. These results suggest that antenatal exposure to a clinically relevant dose of betamethasone impairs renal function in rams. Moreover, angiotensin-(1-7) appears capable of activating the AT1R in uninephrectomized rams.

Original languageEnglish (US)
Pages (from-to)290-298
Number of pages9
JournalJRAAS - Journal of the Renin-Angiotensin-Aldosterone System
Volume14
Issue number4
DOIs
StatePublished - Dec 2013
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health, Grants HD-47584 and HD-17644.

Keywords

  • Angiotensin-(1-7)
  • antenatal betamethasone
  • programming hypertension
  • sodium excretion
  • unilateral nephrectomy

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