Spironolactone, but not enalapril, potentiates hypoxia-inducible factor-1α and ets-1 expression in newborn rat kidney

Hyung-Eun Yim, J. H. Kim, Kee Hwan Yoo, I. S. Bae, Giyoung Jang, Young Sook Hong, J. W. Lee

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Hypoxia is regarded as an important physiological factor that controls nephrogenesis. We investigated whether the reninangiotensin-aldosterone system (RAAS) affects hypoxia-related target genes in developing kidneys. Newborn rat pups were treated with enalapril (30 mg/kg/d) or spironolactone (200 mg/kg/d) for 7 days. Tissue hypoxia was assessed by the uptake of a hypoxyprobe-1, pimonidazole (200 mg/kg), and the expression of hypoxia-responsive genes. In the enalapril group, hypoxia-inducible factor (HIF)-1α, HIF-2α, and Ets-1 protein expression were not changed, compared to the control group. In the spironolactone group, HIF-1α and Ets-1 protein expression were significantly increased by immunoblots and immunohistochemistry, whereas HIF-2α protein expression was not changed, compared to the control group. In the enalapril group, the immunoactivity of pimonidazole was not significantly different from that of the controls. However, in the spironolactone group, pimonidazole staining demonstrated that the cortex and medulla underwent severe hypoxia. In summary, our data showed that aldosterone inhibition in the developing kidney augmented the hypoxic responses, and up-regulated the expression of key mediators of hypoxia including HIF-1α and Ets-1. Angiotensin II inhibition did not affect hypoxia-related alterations in the developing kidney. The components of RAAS may differentially modulate renal hypoxia and its related target genes in the developing rat kidney.

Original languageEnglish
Pages (from-to)74-81
Number of pages8
JournalJournal of Physiology and Pharmacology
Volume61
Issue number1
Publication statusPublished - 2010 Feb 1

Keywords

  • Aldosterone
  • Angiotensin
  • Angiotensin converting enzyme
  • Hypoxia
  • Hypoxia-inducible factor
  • Kidney development

ASJC Scopus subject areas

  • Physiology
  • Pharmacology

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