Endothelin Receptor Blockade in Congestive Heart Failure

To the Editor:Of the many new therapeutic agents for slowing the progression of congestive heart failure (CHF), other than antagonizing the renin-angiotensin-aldosterone system, blocking the endothelin receptors seems to be most promising.The two latest reports published in Circulation 1,2 render further support to this exciting concept.Endothelin may contribute to the symptoms associated with CHF.Patients with the lowest exercise capacity, as measured objectively by maximum oxygen consumption (V ˙O2 max) were those who had the highest plasma levels of endothelin-1 at the time of maximal exercise. 3This finding suggests that endothelin may play a role in limiting the ability of the peripheral vasculature to dilate during exercise and, thus, contribute to exercise intolerance in these patients. 4Therefore, the reduced exercise capacity of patients with CHF may be more than a derangement in central hemodynamic variables, such as decreased cardiac output and increased pulmonary artery wedge pressure.Several endothelin receptor antagonists have been developed.Tezosentan 1 is being developed specifically for the short-term intravenous treatment of acute CHF.Studies with LU135252 2 and bosentan 5 indicate that short-term treatment with bolus intravenous or oral dosages is associated with improved systemic