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Type: Journal article
Title: Inhibition of NHE3-mediated sodium absorption in the gut reduced cardiac end-organ damage without deteriorating renal function in obese spontaneously hypertensive rats
Author: Linz, B.
Hohl, M.
Reil, J.
Böhm, M.
Linz, D.
Citation: Journal of Cardiovascular Pharmacology, 2016; 67(3):225-231
Publisher: Wolters Kluwer Health
Issue Date: 2016
ISSN: 0160-2446
Statement of
Benedikt Linz, Mathias Hohl, Jan Christian Reil, Michael Böhm and Dominik Linz
Abstract: Increased sodium absorption in the gut is one mechanism contributing to hypertensive blood pressure values. The sodium-proton-exchanger subtype 3 (NHE3) is an important mediator of intestinal sodium absorption. The compound SAR is a new specific NHE3 inhibitor with extremely low oral absorbability leading to decreased sodium absorption in the gut and substantial systolic blood pressure reduction. The effects of intestinal NHE3 inhibition on cardiac and renal hypertensive end-organ damage are unknown. The effects of SAR (1 mg·kg⁻¹·d⁻¹ in chow) on left ventricular (LV) and renal remodeling processes were studied by magnetic resonance imaging and biochemical and histological analysis in obese spontaneously hypertensive rats (SHR-ob SAR) compared with placebo-treated SHR-ob (SHR-ob PLAC). Inhibition of intestinal NHE3 by SAR lowered blood pressure and reduced LV end-diastolic pressure from 21 ± 3.0 to 15 ± 2.0 mm Hg (P = 0.0016), whereas heart rate kept unchanged. LV mass indices, LV myocyte diameters, and LV fibrosis formation were lower in SHR-ob SAR compared with SHR-ob PLAC. SAR did not influence urinary albumin to creatinine ratio or glomerular filtration rate. Renal interstitial fibrosis formation, as well as podocyte damage and glomerulosclerosis remained unchanged. Reduction of intestinal sodium absorption by selective NHE3 inhibition in the gut lowered high blood pressure and reduced LV remodeling without deteriorating renal functional and structural parameters in SHR-ob.
Keywords: NHE3 inhibition, intestinal sodium absorption, blood pressure, cardiac remodeling
Rights: Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
RMID: 0030067336
DOI: 10.1097/FJC.0000000000000336
Appears in Collections:Medicine publications

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