Role of the serotonin transporter in pulmonary arterial hypertension.

Pulmonary arterial hypertension is a disease in which pulmonary arterial pressure is raised, leading to right heart failure. Survival is poor despite current therapeutic strategies. The 'serotonin hypothesis of pulmonary arterial hypertension' arose in the 1960s following an 'epidemic' of pulmonary arterial hypertension in women taking the indirect serotinergic agonist aminorex as an anorexigen. In the 1980s, the hypothesis was revisited following the occurrence of pulmonary arterial hypertension associated with the use of fenfluramines as anorexigens; these are also indirect serotinergic agents. Research has identified changes in serotonin synthesis, serotonin receptor activation and serotonin uptake via the serotonin transporter in experimental and clinical pulmonary arterial hypertension. This review will discuss our current understanding of this serotonin hypothesis with particular reference to the role of the serotonin transporter.