Spironolactone and enalapril differentially up-regulate the expression of VEGF and heme oxygenase-1 in the neonatal rat kidney.
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.
Department of Pediatrics, Korea University Medical Center, College of Medicine, Korea University, Seoul 152-703, Korea.
Hyung Eun
HE
Yim
Ji Hae
JH
Kim
Kee Hwan
KH
Yoo
In Sun
IS
Bae
Young Sook
YS
Hong
Joo Won
JW
Lee
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D004656:Enalapril / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D000860:Hypoxia / Q000201:enzymology / Q000235:genetics; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013148:Spironolactone / Q000494:pharmacology*; D013997:Time Factors; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D013148:Spironolactone; D004656:Enalapril; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1