Endothelin-receptor antagonism: the future is bright.

摘要

Pulmonary arterial hypertension is a progressive and debilitating disease characterised by vasoconstriction of the small pulmonary arteries with associated structural changes. Idiopathic pulmonary arterial hypertension is rare (incidence is one to two cases per million) and mainly affects women in their childbearing years. Secondary causes include HIV, connective tissue diseases, and portal hypertension. Treatments for pulmonary arterial hypertension include prostanoids and sildenafil, which are indicated for WHO functional classes II-IV. First discovered 20 years ago,1 endothelin-1 is a potent vasconstrictor with mitogenic and profibrotic properties. Endothelin-1 has been implicated in the pathogenesis of pulmonary arterial hypertension, and endothelin-receptor antagonism is an addition to existing treatment.2 Although endothelin-receptor antagonists— both selective endothelin A and mixed A and B—have been developed, the mixed antagonist bosentan and the selective endothelin A antagonist ambrisentan are the only licensed-antagonists currently available in both Europe and the" USA.