The mechanisms underlying “aldosterone escape,” which refers to the excretion of sodium
(Na+) during high Na+ intake despite inappropriately increased levels of mineralocorticoids,
are incompletely understood. Because local purinergic tone in the aldosterone-sensitive
distal nephron downregulates epithelial Na+ channel (ENaC) activity, we tested whether this
mechanism mediates aldosterone escape. Here, urinary ATP concentration increased with
dietary Na+ intake in mice. Physiologic concentrations of ATP decreased ENaC activity in a …