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Endothelin antagonists in hypertension and kidney disease

Kevin E C Meyers1, Christine Sethna

  • 1Nephrology Division, Department of Pediatrics, The Children's Hospital of Philadelphia, 34th and Civic Center Boulevard, Philadelphia, PA 19104, USA. meyersk@email.chop.edu

Pediatric Nephrology (Berlin, Germany)
|October 17, 2012
PubMed

Insights

The endothelin system contributes to hypertension and diabetic kidney disease. Selective endothelin A receptor blockade shows promise for treatment, but challenges remain.

Area of Science:

  • Nephrology
  • Cardiovascular Medicine
  • Endocrinology

Background:

  • The endothelin (ET) system, particularly endothelin-1 (ET-1), is implicated in hypertension and proteinuric kidney diseases, including diabetic complications.
  • ET-1 acts as a potent vasoconstrictor affecting systemic vasculature and kidneys, with receptors found on various cell types.
  • ET-1 signaling is linked to collagen accumulation, inflammation, extracellular matrix remodeling, and renal fibrosis.

Purpose of the Study:

  • To review the current understanding of the endothelin system's role in hypertension and kidney disease.
  • To summarize the therapeutic potential of endothelin system antagonism.

Main Methods:

  • Literature review of experimental evidence and clinical studies on endothelin receptor blockade.
  • Analysis of the role of ET-1 in the pathogenesis of hypertension and kidney disease.

Main Results:

  • Selective endothelin A receptor (ETAR) blockade shows therapeutic promise for hypertension, proteinuria, and diabetes.
  • Concomitant blockade of the endothelin B receptor (ETBR) may be detrimental, causing vasoconstriction and fluid retention.

Conclusions:

  • Endothelin receptor antagonists are potential treatments, but selectivity issues and side effects require further investigation.
  • Targeting the ET system, specifically ETAR, offers a promising avenue for managing complex cardiovascular and renal conditions.

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