Overexpression of HIF-1¦Á transgene in the renal medulla attenuated salt sensitive hypertension in Dahl S rats

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• 作者：Qing Zhu ; Zhengchao Wang¹ ; Min Xia ; Pin-Lan Li ; Fan Zhang ; Ningjun Li ; ^nli@vcu.edu
• 关键词：Pressure natriuresis ; Heme oxygenase-1 ; Cyclooxygenase-2 ; Sodium excretion
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Basis of Disease
• 出版年：2012
• 出版时间：June, 2012
• 年：2012
• 卷：1822
• 期：6
• 页码：936-941
• 全文大小：684 K

文摘

Hypoxia inducible factor (HIF)-1¦Á-mediated gene activation in the renal medulla in response to high salt intake plays an important role in the control of salt sensitivity of blood pressure. High salt-induced activation of HIF-1¦Á in the renal medulla is blunted in Dahl S rats. The present study determined whether the impairment of the renal medullary HIF-1¦Á pathway was responsible for salt sensitive hypertension in Dahl S rats. Renal medullary HIF-1¦Á levels were induced by either transfection of HIF-1¦Á expression plasmid or chronic infusion of CoCl₂ into the renal medulla, which was accompanied by increased expressions of anti-hypertensive genes, cyclooxygenase-2 and heme oxygenase-1. Overexpression of HIF-1¦Á transgenes in the renal medulla enhanced the pressure natriuresis, promoted the sodium excretion and reduced sodium retention after salt overload. As a result, hypertension induced by 2-week high salt was significantly attenuated in rats treated with HIF-1¦Á plasmid or CoCl₂. These results suggest that an abnormal HIF-1¦Á in the renal medulla may represent a novel mechanism mediating salt-sensitive hypertension in Dahl S rats and that induction of HIF-1¦Á levels in the renal medulla could be a therapeutic approach for the treatment of salt-sensitive hypertension.