title: Deficiency of renal cortical EGF increases ENaC activity and contributes to salt-sensitive hypertension.
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.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
authors.forename: Tengis S
authors.initials: TS
authors.lastname: Pavlov
authors.forename: Vladislav
authors.initials: V
authors.lastname: Levchenko
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'Connor
authors.forename: Daria V
authors.initials: DV
authors.lastname: Ilatovskaya
authors.forename: Oleg
authors.initials: O
authors.lastname: Palygin
authors.forename: Takefumi
authors.initials: T
authors.lastname: Mori
authors.forename: David L
authors.initials: DL
authors.lastname: Mattson
authors.forename: Andrey
authors.initials: A
authors.lastname: Sorokin
authors.forename: Julian H
authors.initials: JH
authors.lastname: Lombard
authors.forename: Allen W
authors.initials: AW
authors.lastname: Cowley
authors.forename: Alexander
authors.initials: A
authors.lastname: Staruschenko
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D020303:Rats, Inbred Dahl; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D053503:Epithelial Sodium Channels; D017673:Sodium Chloride, Dietary; C013407:benzamil; D004815:Epidermal Growth Factor; D000584:Amiloride