Figure 7.

Schematic illustration of ENaC regulation by NOX4 in the Dahl SS rats. Elevated expression of NOX4 in hypertension and diabetic conditions increases H₂O₂ level in the interstitium and on the luminal side. Oxidative stress acts via intracellular pathways (such as modulation of expression and activity of EGF Receptor, PGE₂, small GTPase Rac1, and other signaling pathways) to elevate expression of ENaC on the apical membrane (19). Apical H₂O₂ production in diabetes facilitates ENaC open probability presumably by activation of PI3-kinase signaling.