Faculty Collaboration Database

Deficiency of renal cortical EGF increases ENaC activity and contributes to salt-sensitive hypertension. J Am Soc Nephrol 2013 Jun;24(7):1053-62

Date

04/20/2013

Pubmed ID

23599382

Pubmed Central ID

PMC3699826

DOI

10.1681/ASN.2012080839

Scopus ID

2-s2.0-84879580245 (requires institutional sign-in at Scopus site)   70 Citations

Abstract

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.

Author List

Pavlov TS, Levchenko V, O'Connor PM, Ilatovskaya DV, Palygin O, Mori T, Mattson DL, Sorokin A, Lombard JH, Cowley AW Jr, Staruschenko A

Authors

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin
Andrey Sorokin PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amiloride
Animals
Blood Pressure
Disease Models, Animal
Epidermal Growth Factor
Epithelial Sodium Channels
Hypertension
Kidney
Rats
Rats, Inbred Dahl
Sodium Chloride, Dietary