Pulmonary hypertension, anorexigens and 5-HT: pharmacological synergism in action?

In pulmonary hypertension (PHT), pulmonary vascular resistance is elevated as a result of increased pulmonary vascular tone and pulmonary vascular remodelling. Certain diet pills, such as the fenfluramines, have been associated with the development of PHT. This class of drugs act as indirect 5-HT receptor agonists and can inhibit 5-HT reuptake and cause the release of 5-HT from platelets. Many pulmonary vasoconstrictors, including 5-HT, activate both Gi- and Gq-linked receptors. Increasing evidence suggests that Gq activation might amplify Gi-linked intracellular pathways to 'uncover' or potentiate vasoconstrictor responses - a phenomenon known as pharmacological synergism, which occurs in the pulmonary circulation. In this review the evidence that 5-HT plays a role in PHT and that pharmacological synergism might contribute to its pathology is discussed.