A Review of Serotonin in the Developing Lung and Neonatal Pulmonary Hypertension

Serotonin (5-HT) is a bioamine that has been implicated in the pathogenesis of pulmonary hypertension (PH). The lung serves as an important site of 5-HT synthesis, uptake, and metabolism with signaling primarily regulated by tryptophan hydroxylase (TPH), the 5-HT transporter (SERT), and numerous unique 5-HT receptors. The 5-HT hypothesis of PH was first proposed in the 1960s and, since that time, preclinical and clinical studies have worked to elucidate the role of 5-HT in adult PH. Over the past several decades, accumulating evidence from both clinical and preclinical studies has suggested that the 5-HT signaling pathway may play an important role in neonatal cardiopulmonary transition and the development of PH in newborns. The expression of TPH, SERT, and the 5-HT receptors is developmentally regulated, with alterations resulting in pulmonary vasoconstriction and pulmonary vascular remodeling. However, much remains unknown about the role of 5-HT in the developing and newborn lung. The purpose of this review is to discuss the implications of 5-HT on fetal and neonatal pulmonary circulation and summarize the existing preclinical and clinical literature on 5-HT in neonatal PH.