title: Renin angiotensin antagonists normalize aberrant activation of epithelial sodium channels in sodium-sensitive hypertension.
abstract: Epithelial sodium channels (ENaC) are ion transporters in the aldosterone-sensitive distal nephron that play an important role in sodium reabsorption in the terminal nephron. Our study of inbred C57Bl6/J mice given a high-sodium diet showed increased ENaC expression accompanied by tubular renin activation on qRT-PCR of laser-captured tubule specimens and Western blotting of membrane proteins, despite inhibition of aldosterone. Treatment with an angiotensin-converting-enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) effectively lowered blood pressure. In addition to lowering blood pressure, ACEI and ARB inhibition downregulated ENaC and renin expression in renal tubules. These effects would act to suppress sodium reabsorption via ENaC and normalize molecular mechanisms that elevate blood pressure in response to increased salt intake.
authors.affiliation: Department of Medical Science and Cardio-Renal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Hisako
authors.initials: H
authors.lastname: Ushio-Yamana
authors.forename: Shintaro
authors.initials: S
authors.lastname: Minegishi
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ishigami
authors.forename: Naomi
authors.initials: N
authors.lastname: Araki
authors.forename: Masanari
authors.initials: M
authors.lastname: Umemura
authors.forename: Koichi
authors.initials: K
authors.lastname: Tamura
authors.forename: Emi
authors.initials: E
authors.lastname: Maeda
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kakizoe
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kitamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Umemura
mesh_terms: D000450:Aldosterone / Q000097:blood; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D015536:Down-Regulation; D053503:Epithelial Sodium Channels / Q000096:biosynthesis / Q000187:drug effects*; D000077545:Eplerenone; D006973:Hypertension / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D020913:Perindopril / Q000494:pharmacology*; D012083:Renin / Q000378:metabolism; D012964:Sodium / Q000652:urine; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D053503:Epithelial Sodium Channels; D007093:Imidazoles; D000451:Mineralocorticoid Receptor Antagonists; D017673:Sodium Chloride, Dietary; D013777:Tetrazoles; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone; C437965:olmesartan; D012964:Sodium; D012083:Renin; D020913:Perindopril