Update on Endothelin Receptor Antagonists in Hypertension.

PURPOSE OF REVIEW: To review the most recent data on the development of endothelin receptor antagonists (ERAs) for the treatment of hypertension and the management of diabetic nephropathy RECENT FINDINGS: Recent reviews and meta-analyses of experimental and clinical data obtained with ERAs confirmed that endothelin receptor blockade is associated with significant decreases in blood pressure in essential hypertension but also in resistant hypertension. In addition, in patients with diabetic nephropathy, ERAs induce significant 30-40% decreases in albuminuria when administered on top of blockers of the renin-angiotensin system. Yet, the benefits of ERAs have often been limited by their tolerability profile, essentially fluid retention and the development of edema and liver toxicity. Hence, several programs have been interrupted. Today, only one ERA, aprocitentan, is still under development for the treatment of resistant hypertension. Regarding the place of ERAs in the management of diabetic nephropathy, the results of the SONAR trial with atrasentan are eagerly awaited but the recent interruption of this trial because of insufficient events is worrisome, as one might not obtain all the expected information for this major trial. Blockade of endothelin receptor have a high potential in the treatment of hypertension and the prevention of the progression of renal diseases such as diabetic nephropathy. Today, the number of clinical programs investigating the potential benefits of ERAs is limited and more data must be obtained to define the real place of ERAs in these indications.