Current therapeutic targets in pulmonary arterial hypertension. Current therapy for PAH targets imbalance of three mediators including ET-1, NO, and PGI2. These pathways become dysregulated in patients with PAH, leading to enhanced vasoconstriction, in situ thrombosis, and pulmonary vascular remodeling. A transverse section of a remodeled pulmonary artery in a patient with PAH is shown, demonstrating intimal proliferation and medial thickening. Patients with PAH have increased levels of the potent vasoconstrictor ET-1 and decreased levels of endothelial vasodilators NO and PGI2 leading to aberrant PASMC proliferation and hypertrophy. Current therapy with endothelin-receptor antagonists, phosphodiesterase inhibitors, and prostacylin analogues aims to reestablish the balance of these vascular effectors. Plus signs (+) indicate an increase in the concentration; minus signs (−) denote a decrease in the concentration, inhibition of an enzyme, or blockage of a receptor. cGMP, cyclic guanosine monophospate; cAMP, cyclic adenosine monophospate. Reproduced from (Humbert et al. 2004) by permission of the Massachusetts Medical Society. Copyright © [2004] Massachusetts Medical Society. All rights reserved.