TY - JOUR
T1 - Deficiency of renal cortical EGF increases ENaC activity and contributes to salt-sensitive hypertension
AU - Pavlov, Tengis S.
AU - Levchenko, V.
AU - O'Connor, Paul M.
AU - Ilatovskaya, Daria V.
AU - Palygin, Oleg
AU - Mori, Takefumi
AU - Mattson, David L.
AU - Sorokin, Andrey
AU - Lombard, Julian H.
AU - Cowley, Allen W.
AU - Staruschenko, Alexander
PY - 2013/6/28
Y1 - 2013/6/28
N2 - 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 lowsalt 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.
AB - 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 lowsalt 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.
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U2 - 10.1681/ASN.2012080839
DO - 10.1681/ASN.2012080839
M3 - Article
C2 - 23599382
AN - SCOPUS:84879580245
SN - 1046-6673
VL - 24
SP - 1053
EP - 1062
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 7
ER -