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The endothelin system and endothelin receptor antagonists

Karin A M Jandeleit-Dahm1, Anna M D Watson

  • 1Diabetes Complications Division - Diabetes and Kidney Disease, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia. Karin.Jandeleit-Dahm@bakeridi.edu.au

Current Opinion in Nephrology and Hypertension
|November 30, 2011
PubMed
Abstract

Insights

Endothelin receptor blockade, particularly ET(A) blockade, shows promise in protecting against kidney disease and blood vessel issues in diabetes. Further research is needed to address potential adverse effects.

Area of Science:

  • Nephrology
  • Cardiovascular Medicine
  • Endocrinology

Background:

  • Endothelin receptor blockade, especially targeting the ET(A) receptor, is increasingly recognized for its protective effects in proteinuric renal disease and diabetes.
  • Evidence suggests these therapies also offer vasculoprotection, impacting cardiovascular health.

Purpose of the Study:

  • To review the evidence for endothelin receptor blockade, specifically ET(A) receptor blockade, in managing proteinuric renal disease and associated vasculopathy in diabetic patients.
  • To evaluate the therapeutic potential and challenges of ET(A) receptor blockade in chronic kidney disease, proteinuria, and atherosclerosis.

Main Methods:

  • Review of recent clinical trials and scientific literature on endothelin receptor blockade.
  • Analysis of the mechanisms underlying the renoprotective and vasculoprotective effects of ET(A) receptor antagonists.
  • Assessment of adverse effects associated with endothelin receptor blockade therapies.

Main Results:

  • Clinical trials indicate that ET(A) receptor blockade holds significant promise for treating proteinuria and chronic kidney disease.
  • These therapies have shown potential in managing atherosclerosis, but adverse effects remain a concern.
  • Endothelin receptor blockade effectively reduces proteinuria, partly by inhibiting inflammatory, oxidative stress, and profibrotic pathways.

Conclusions:

  • Endothelin receptor blockade significantly attenuates proteinuria through the inhibition of key inflammatory and oxidative stress pathways.
  • Combining ET(A) receptor blockade with existing treatments like ACE inhibitors or ARBs may offer enhanced or synergistic renoprotection and vasculoprotection.
  • These benefits are particularly relevant in managing hypertension and diabetes, suggesting a broader role in cardiovascular and renal protection.

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