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      Endothelin-a receptor antagonism after renal angioplasty enhances renal recovery in renovascular disease.

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          Abstract

          Percutaneous transluminal renal angioplasty/stenting (PTRAS) is frequently used to treat renal artery stenosis and renovascular disease (RVD); however, renal function is restored in less than one half of the cases. This study was designed to test a novel intervention that could refine PTRAS and enhance renal recovery in RVD. Renal function was quantified in pigs after 6 weeks of chronic RVD (induced by unilateral renal artery stenosis), established renal damage, and hypertension. Pigs with RVD then underwent PTRAS and were randomized into three groups: placebo (RVD+PTRAS), chronic endothelin-A receptor (ET-A) blockade (RVD+PTRAS+ET-A), and chronic dual ET-A/B blockade (RVD+PTRAS+ET-A/B) for 4 weeks. Renal function was again evaluated after treatments, and then, ex vivo studies were performed on the stented kidney. PTRAS resolved renal stenosis, attenuated hypertension, and improved renal function but did not resolve renal microvascular rarefaction, remodeling, or renal fibrosis. ET-A blocker therapy after PTRAS significantly improved hypertension, microvascular rarefaction, and renal injury and led to greater recovery of renal function. Conversely, combined ET-A/B blockade therapy blunted the therapeutic effects of PTRAS alone or PTRAS followed by ET-A blockade. These data suggest that ET-A receptor blockade therapy could serve as a coadjuvant intervention to enhance the outcomes of PTRAS in RVD. These results also suggest that ET-B receptors are important for renal function in RVD and may contribute to recovery after PTRAS. Using clinically available compounds and techniques, our results could contribute to both refinement and design of new therapeutic strategies in chronic RVD.

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          Author and article information

          Journal
          J. Am. Soc. Nephrol.
          Journal of the American Society of Nephrology : JASN
          1533-3450
          1046-6673
          May 2015
          : 26
          : 5
          Affiliations
          [1 ] Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, Department of Medicine, and Department of Radiology, University of Mississippi Medical Center, Jackson, Mississippi achade@umc.edu.
          [2 ] Department of Physiology and Biophysics.
          Article
          ASN.2014040323
          10.1681/ASN.2014040323
          25377076
          64e370db-2d86-49d8-bd11-e64cd3cc4639
          Copyright © 2015 by the American Society of Nephrology.
          History

          angioplasty,endothelin-1,imaging,microcirculation,renal artery stenosis

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