The endothelin system and endothelin receptor antagonists.

PURPOSE OF REVIEW

There is increasing evidence that endothelin receptor blockade and, in particular, ET(A) receptor blockade not only confers protection against proteinuric renal disease in diabetes but also confers vasculoprotection.

RECENT FINDINGS

Recent clinical trials using ET(A) receptor blockade in treating proteinuria and chronic kidney disease as well as atherosclerosis show great promise; however, adverse effects are still problematic.

SUMMARY

Endothelin receptor blockade is associated with a significant attenuation of proteinuria and these effects are mediated in part via inhibition of inflammatory and oxidative stress related pathways as well profibrotic pathways. The addition of ET(A) receptor blockade to currently established therapies such as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may result in additional or synergistic renoprotection and vasculoprotection in hypertension and, in particular, in the context of diabetes.