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.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Linz B,Hohl M,Reil JC,Böhm M,Linz Ddoi
10.1097/FJC.0000000000000336subject
Has Abstractpub_date
2016-03-01 00:00:00pages
225-31issue
3eissn
0160-2446issn
1533-4023journal_volume
67pub_type
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journal_title:Journal of cardiovascular pharmacology
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