Fig. 6.
Hypothetical working model of ENaC negative feedback regulation. With an increase in acute high shear stress, ENaC in the apical membrane of the collecting duct initially leads to the stimulation of ET-1 and the ETB receptor resulting in an increase in NO via NOS1. There is also a small but significant increase in NOS3-derived NO; however, it is the NOS1-derived NO that acts in a negative feedback loop to decrease ENaC Po and promotes natriuresis. The downstream targets of NOS3-derived NO remain to be elucidated.