Treating pulmonary arterial hypertension: current treatments and future prospects.

Pulmonary arterial hypertension (PAH) consists of a group of heterogeneous but distinct disorders characterized by complex proliferation of the pulmonary vascular endothelium and progressive pulmonary vascular remodeling that leads to right ventricular failure and death. Over the past two decades, significant advances in our understanding of the pathobiology of PAH have led to the development of several therapeutic targets in this disease. Besides conservative therapeutic strategies such as anticoagulation and diuretics, the current treatment paradigm for PAH targets the mediators of the three main biologic pathways that are critical for its pathogenesis and progression: endothelin receptor antagonists inhibit the upregulated endothelin pathway by blocking the biologic activity of endothelin-1; phosphodiesterase-5 inhibitors prevent breakdown and increase the endogenous availability of cyclic guanosine monophosphate, which signals the vasorelaxing effects of the downregulated mediator nitric oxide; and prostacyclin derivatives provide an exogenous supply of the deficient mediator prostacyclin. In addition to these established current therapeutic options, a large number of potential therapeutic targets are being investigated. These novel therapeutic targets include soluble guanylyl cyclase, phosphodiesterases, tetrahydrobiopterin, 5-hydroxytryptamine (serotonin) receptor 2B, vasoactive intestinal peptide, receptor tyrosine kinases, adrenomedullin, rho kinase, elastases, endogenous steroids, endothelial progenitor cells, immune cells, bone morphogenetic protein and its receptors, potassium channels, metabolic pathways, and nuclear factor of activated T cells. This review provides an overview of the current therapeutic options and potential therapeutic targets for PAH.