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

Hypoxia inducible factor (HIF)-1α-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-1α in the renal medulla is blunted in Dahl S rats. The present study determined whether the impairment of the renal medullary HIF-1α pathway was responsible for salt sensitive hypertension in Dahl S rats. Renal medullary HIF-1α levels were induced by either transfection of HIF-1α 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-1α 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-1α plasmid or CoCl2. These results suggest that an abnormal HIF-1α in the renal medulla may represent a novel mechanism mediating salt-sensitive hypertension in Dahl S rats and that induction of HIF-1α levels in the renal medulla could be a therapeutic approach for the treatment of salt-sensitive hypertension.

► High salt-induced HIF-1α activation in the renal medulla is blunted in Dahl S rat. ► Induction of HIF-1α increased the expressions of anti-hypertensive genes. ► Induction of HIF-1α in the renal medulla enhanced sodium excretion. ► Induction of HIF-1α in the renal medulla attenuated salt-sensitive hypertension. ► Abnormal HIF-1α in the renal medulla is the cause for salt-sensitive hypertension.