Various stimuli, including
hormones and
growth factors, modulate
epithelial sodium channels (ENaCs), which fine-tune Na(+) absorption in the kidney. Members of the
EGF family are important for maintaining transepithelial Na(+) transport, but whether
EGF influences ENaC, perhaps mediating
salt-sensitive
hypertension, is not well understood. Here, the ENaC inhibitor
benzamil attenuated the development of
hypertension in Dahl salt-sensitive rats. Feeding these
salt-sensitive rats a high-
salt diet led to lower levels of
EGF in the kidney cortex and enhanced the expression and activity of ENaC compared with feeding a
low-salt diet. To directly evaluate the role of
EGF in the development of
hypertension and its effect on ENaC activity, we infused
EGF intravenously while continuously monitoring BP of the
salt-sensitive rats. Infusion of
EGF decreased ENaC activity, prevented the development of
hypertension, and attenuated glomerular and renal tubular damage. Taken together, these findings indicate that cortical
EGF levels decrease with a high-
salt diet in
salt-sensitive rats, promoting ENaC-mediated Na(+) reabsorption in the collecting duct and the development of
hypertension.