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
04/20/2013Pubmed ID
23599382Pubmed Central ID
PMC3699826DOI
10.1681/ASN.2012080839Scopus ID
2-s2.0-84879580245 (requires institutional sign-in at Scopus site) 64 CitationsAbstract
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 AAuthors
Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of WisconsinAndrey Sorokin PhD Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AmilorideAnimals
Blood Pressure
Disease Models, Animal
Epidermal Growth Factor
Epithelial Sodium Channels
Hypertension
Kidney
Rats
Rats, Inbred Dahl
Sodium Chloride, Dietary