Endothelin receptor antagonists in pulmonary arterial hypertension

Abstract

The endothelin (ET) system, especially ET-1 and the ETA and ETB receptors, has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Together with prostanoids and phosphodiesterase 5 inhibitors, ET receptor antagonists have become mainstays in the current treatment of PAH. Three substances are currently available for the treatment of PAH. One of these substances, bosentan, blocks both ETA and ET B receptors, whereas the two other compounds, sitaxsentan and ambrisentan, are more selective blockers of the ETA receptor. There is ongoing debate as to whether selective or nonselective ET receptor blockade is advantageous in the setting of PAH, although there is no clear evidence that receptor selectivity is relevant with regard to the clinical effects of these drugs. For the time being, other features, such as safety profiles and the potential for pharmacokinetic interactions with other drugs used in the treatment of PAH, may be more important than selectivity or nonselectivity when selecting treatments for individual patients. Copyright©ERS Journals Ltd 2008.