Silencing of Hypoxia-Inducible Factor-1α Gene Attenuated Angiotensin II–Induced Renal Injury in Sprague-Dawley Rats

• DOI: 10.1161/hypertensionaha.111.177626
• Publication Date: 2011-09-07T04:16:36Z
• Authors: Qing Zhu; Zhengchao Wang; Min Xia; Pin-Lan Li; Benjamin W. Van T...; Antonio Abbate; Romesh Dhaduk; Ningjun Li
• Keywords: Hypoxia-Inducible Factors; Hypoxia

Although it has been shown that upregulation of hypoxia-inducible factor (HIF)-1α is protective in acute ischemic renal injury, long-term overactivation HIF-1α implicated to be injurious chronic kidney diseases. Angiotensin II (Ang II) a well-known pathogenic producing injury and also increase HIF-1α. However, the contribution Ang II-induced not evidenced. The present study tested hypothesis mediates Sprague-Dawley rats. Chronic was induced by infusion (200 ng/kg per minute) for 2 weeks uninephrectomized Transfection vectors expressing small hairpin RNA into kidneys knocked down gene expression 70%, blocked activation, significantly attenuated albuminuria, which accompanied inhibition vascular endothelial growth factor, known glomerular permeability glomeruli. improved morphological damage II. Furthermore, collagen α-smooth muscle actin tubulointerstitial region. There no difference creatinine clearance blood pressure. had effect on reduction flow hypoxia kidneys. These data suggested HIF-1α-mediated regulation pathway mediating injuries, normalization overactivated may used as treatment strategy damages associated with excessive