The endothelin system and endothelin receptor antagonists

Purpose of review There is increasing evidence that endothelin receptor blockade and, in particular, ETA receptor blockade not only confers protection against proteinuric renal disease in diabetes but also confers vasculoprotection. Recent findings Recent clinical trials using ETA 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 ETA 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.