Figure 1.

HIF-1α-mediated gene activation in the molecular adaptation to high salt intake in the renal medulla and its role in salt sensitive hypertension. High salt intake inhibits PHD2, an enzyme promoting HIF-1α degradation, leading to the accumulation of HIF-1α in the renal medulla. HIF-1α then activates its target genes such as NOS2, HO-1 and COX-2, which augment the production of anti-hypertensive factors in the renal medulla to remove the extra sodium load, thereby, maintaining a normal blood pressure after high salt challenge. However, in Dahl/ss rats, high salt-induced inhibition of PHD2 is absent. Therefore, there is no HIF-1α accumulation and neither the activation of anti-hypertensive genes in the renal medulla after high salt challenge, which impairs the capability of the kidneys to remove extra sodium load and results in sodium retention, consequently, producing a salt sensitive hypertension in this animal model.