Pulmonary arterial hypertension (PAH) encompasses a group of disorders in which vascular obliteration at the level of the small pulmonary arteries results in progressive elevation of the pulmonary pressure and pulmonary vascular resistance, right ventricular failure and death. PAH includes idiopathic PAH (IPAH, formerly primary pulmonary hypertension, (PPH)), familial PAH, PAH associated with collagen vascular disease, congenital systemic-to-pulmonary shunts, portal hypertension, HIV infection, drug and toxins and other conditions, PAH associated with significant venous or capillary involvement and persistent pulmonary hypertension of the newborn.1 The natural history of PAH is characterised by progressive dyspnoea and decreased exercise tolerance, associated with advancing right ventricular dysfunction and premature death.2 Current medical therapy provides symptomatic benefit, increases exercise capacity and delays the clinical progression of the disease. Improved life expectancy with therapy has also been reported in retrospective studies. Treatment choices in PAH are dictated by disease severity, the specific type of PAH, the presence of active vasoreactivity and by the patient’s ability to use medications with complex modes of administration.

Goals of specific PAH therapy are reduction of pulmonary pressure and pulmonary vascular resistance, inhibition or reversal of pulmonary vascular remodelling and improvement of right ventricular function. Vascular wall remodelling and proliferation are the hallmark of pulmonary arterial obstruction in PAH. Central to the pathogenesis of vascular remodelling is the dysfunction of the pulmonary vascular endothelium with an imbalance between endothelial mediators with opposing actions (i.e. vasoconstriction–proliferation versus vasodilation–antiproliferation) on the pulmonary vasculature. Prostacyclin is an endogenous metabolite of arachidonic acid produced by the vascular endothelium, with pulmonary and systemic vasodilator properties and antiplatelet antiaggregatory action.3 In vitro studies have demonstrated the antiproliferative effect of prostacyclin on the vascular smooth muscle cells. Relative deficiency of prostacyclin has an important role in the pathogenesis of PAH and administration of exogenous prostanoid analogues by various routes represents an important therapeutic strategy in PAH.