Therapeutic Implications

Targeting the endothelin pathway has become a cornerstone of pulmonary hypertension treatment. Endothelin receptor antagonists (ERAs) are designed to block the harmful effects of EDN1 while preserving beneficial pathways where possible:

• Selective ETA Antagonists (e.g., ambrisentan) reduce vasoconstriction and smooth muscle proliferation.
• Dual ETA/ETB Antagonists (e.g., bosentan, macitentan) provide broader inhibition but must balance ETB-mediated vasodilation.

ERAs have been shown to improve exercise capacity, hemodynamics, and time to clinical worsening in PAH patients, representing a direct translation of molecular insights into effective therapy.