Endothelin in health and disease: endothelin receptor antagonists in the management of pulmonary artery hypertension.

Endothelin (ET) has been identified as playing a fundamental role in many disease processes. Therapeutic efforts at interrupting ET's pathologic effects have focused on endothelin receptor antagonists (ERAs), of which two, bosentan and sitaxsentan, have been evaluated for the treatment of both primary and secondary pulmonary arterial hypertension (PAH). We discuss the multiple actions of ET, its role in various disease states, and the effects of ET receptor stimulation and blockade. Current classification and management of PAH are reviewed, along with the promise of greatly improved treatment generated by recent and ongoing clinical trials using ERAs.