Spironolactone and enalapril differentially up-regulate the expression of VEGF and heme oxygenase-1 in the neonatal rat kidney

Hyung-Eun Yim, Ji Hae Kim, Kee Hwan Yoo, In Sun Bae, Young Sook Hong, Joo Won Lee

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Both the renin-angiotensin-aldosterone system (RAAS) and hypoxia are vital physiological factors involved in the control of nephrogenesis and vascularization. We investigated the relationship between RAAS and hypoxia in the developing kidney. The expression of VEGF and heme oxygenase (HO)-1 related with the oxygen was analyzed in the enalapril-or spironolactone-treated neonatal rat kidneys. Enalapril (30 mg/kg/d) or spironolactone (200 mg/kg/d) was administered to newborn rat pups for 7 d. The newborn rats were injected i.p. with pimonidazole (200 mg/kg), a marker of severe tissue hypoxia, 1 h before killing. VEGF and HO-1 protein expression was significantly increased by immunoblots and immunohistochemistry in both the enalapril-and spironolactone-treated kidneys, compared with the controls (p < 0.05). HO-1 mRNA expression was increased in the spironolactone-treated group (p < 0.05). The immunoactivity of pimonidazole was not different from that of the controls in the enalapril-treated group, whereas it was increased in the spironolactone-treated group. The results of this study indicate that aldosterone blockade or angiotensin II inhibition in the developing rat kidney up-regulated renal VEGF and HO-1 expression regardless of the hypoxic conditions and may differentially modulate VEGF and HO-1 production.

Original languageEnglish
Pages (from-to)378-383
Number of pages6
JournalPediatric Research
Issue number5 PART 1
Publication statusPublished - 2011 May 1


ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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