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Hypertension. 2016 Jan;67(1):130-8. doi: 10.1161/HYPERTENSIONAHA.115.06530. Epub 2015 Nov 9.

Deoxycorticosterone Acetate/Salt-Induced Cardiac But Not Renal Injury Is Mediated By Endothelial Mineralocorticoid Receptors Independently From Blood Pressure.

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  • 1From the Department of Cardiology and Angiology I, Heart Center (A.L., I.H., C.B., M.M.), Institute of Experimental and Clinical Pharmacology and Toxicology (A.L., D.F., S.B., R.G., L.H.), Renal Division, Department of Medicine (F.G., T.B.H.), and BIOSS Centre for Biological Signaling Studies (T.B.H., L.H.), University of Freiburg, Freiburg, Germany. achim.lother@universitaets-herzzentrum.de lutz.hein@pharmakol.uni-freiburg.de.
  • 2From the Department of Cardiology and Angiology I, Heart Center (A.L., I.H., C.B., M.M.), Institute of Experimental and Clinical Pharmacology and Toxicology (A.L., D.F., S.B., R.G., L.H.), Renal Division, Department of Medicine (F.G., T.B.H.), and BIOSS Centre for Biological Signaling Studies (T.B.H., L.H.), University of Freiburg, Freiburg, Germany.

Abstract

Chronic kidney disease has a tremendously increasing prevalence and requires novel therapeutic approaches. Mineralocorticoid receptor (MR) antagonists have proven highly beneficial in the therapy of cardiac disease. The cellular and molecular events leading to cardiac inflammation and remodeling are proposed to be similar to those mediating renal injury. Thus, this study was designed to evaluate and directly compare the effect of MR deletion in endothelial cells on cardiac and renal injury in a model of deoxycorticosterone acetate-induced hypertension. Endothelial MR deletion ameliorated deoxycorticosterone acetate/salt-induced cardiac remodeling. This was associated with a reduced expression of the vascular cell adhesion molecule Vcam1 in MR-deficient cardiac endothelial cells. Ambulatory blood pressure telemetry revealed that the protective effect of MR deletion was independent from blood pressure. Similar to the heart, deoxycorticosterone acetate/salt-induced severe renal injury, including inflammation, fibrosis, glomerular injury, and proteinuria. However, no differences in renal injury were observed between genotypes. In conclusion, MR deletion from endothelial cells ameliorated deoxycorticosterone acetate/salt-induced cardiac inflammation and remodeling independently from alterations in blood pressure but it did not affect renal injury. These findings suggest that the anti-inflammatory mechanism mediating organ protection after endothelial cell MR deletion is specific for the heart versus the kidney.

© 2015 American Heart Association, Inc.

KEYWORDS:

aldosterone; endothelial cells; heart failure; hypertension; kidney diseases; mineralocorticoid receptor

PMID:
26553231
[PubMed - indexed for MEDLINE]
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