Rats were uninephrectomized one week before, and the remaining left kidney was transfected with 50 µg plasmids into the renal medulla using in vivo-jetPEI in combination with ultrasound radiation.

Hypoxia inducible factor (HIF)-1alpha-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-1alpha in the renal medulla is blunted in Dahl S rats. The present study determined whether the impairment of the renal medullary HIF-1alpha pathway was responsible for salt sensitive hypertension in Dahl S rats. Renal medullary HIF-1alpha levels were induced by either transfection of HIF-1alpha expression plasmid or chronic infusion of CoCl(2) into the renal medulla, which was accompanied by increased expressions of anti-hypertensive genes, cyclooxygenase-2 and heme oxygenase-1. Overexpression of HIF-1alpha 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-1alpha plasmid or CoCl(2). These results suggest that an abnormal HIF-1alpha in the renal medulla may represent a novel mechanism mediating salt-sensitive hypertension in Dahl S rats and that induction of HIF-1alpha levels in the renal medulla could be a therapeutic approach for the treatment of salt-sensitive hypertension.