Drug Insight: endothelin-receptor antagonists for pulmonary arterial hypertension in systemic rheumatic diseases.

Rapid advances in the understanding of endothelin as a naturally occurring peptide with developmental and regulatory roles in normal physiology, along with a number of deleterious effects under pathologic conditions (including vasoconstriction, fibrosis, vascular hypertrophy, and inflammation) have led to the development of endothelin-receptor antagonists (ERAs). Bosentan, an antagonist with dual specificity for the endothelin-receptor subtypes A and B, has been shown to be efficacious and well tolerated in placebo-controlled clinical trials and is now approved in many countries, including the US, Canada, and Europe, for treatment of pulmonary arterial hypertension (PAH), including PAH associated with rheumatic diseases. ERAs with specificity for the endothelin-receptor subtype A, including sitaxsentan and ambrisentan, are currently undergoing investigation. This article reviews PAH associated with systemic rheumatic diseases and describes the role of ERAs in this setting.