{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:45:14Z","timestamp":1790801114548,"version":"4.1.0"},"reference-count":67,"publisher":"American Physiological Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2013,6,15]]},"abstract":"<jats:p>Although past studies demonstrate that altered serotonin (5-HT) signaling is present in adults with idiopathic pulmonary arterial hypertension, whether serotonin contributes to the pathogenesis of persistent pulmonary hypertension of the newborn (PPHN) is unknown. We hypothesized that 5-HT contributes to increased pulmonary vascular resistance (PVR) in a sheep model of PPHN and that selective 5-HT reuptake inhibitor (SSRI) treatment increases PVR in this model. We studied the hemodynamic effects of 5-HT, ketanserin (5-HT<jats:sub>2A<\/jats:sub>receptor antagonist), and sertraline, an SSRI, on pulmonary hemodynamics of the late gestation fetal sheep with PPHN caused by prolonged constriction of the ductus arteriosis. Brief intrapulmonary infusions of 5-HT increased PVR from 1.0 \u00b1 0.07 (baseline) to 1.4 \u00b1 0.22 mmHg\/ml per minute of treatment ( P &lt; 0.05). Ketanserin decreased PVR from 1.1 \u00b1 0.15 (baseline) to 0.82 \u00b1 0.09 mmHg\/ml per minute of treatment ( P &lt; 0.05). Sertraline increased PVR from 1.1 \u00b1 0.17 (baseline) to 1.4 \u00b1 0.17 mmHg\/ml per minute of treatment ( P = 0.01). In addition, we studied 5-HT production and activity in vitro in experimental PPHN. Compared with controls, pulmonary artery endothelial cells from fetal sheep with PPHN exhibited increased expression of tryptophan hydroxylase 1 and 5-HT production by twofold and 56%, respectively. Compared with controls, 5-HT<jats:sub>2A<\/jats:sub>R expression was increased in lung homogenates and pulmonary artery smooth muscle cell lysates by 35% and 32%, respectively. We concluded that increased 5-HT contributes to high PVR in experimental PPHN through activation of the 5-HT<jats:sub>2A<\/jats:sub>receptor and that SSRI infusion further increases PVR in this model.<\/jats:p>","DOI":"10.1152\/ajplung.00043.2013","type":"journal-article","created":{"date-parts":[[2013,4,20]],"date-time":"2013-04-20T03:00:17Z","timestamp":1366426817000},"page":"L894-L901","source":"Crossref","is-referenced-by-count":40,"title":["Serotonin contributes to high pulmonary vascular tone in a sheep model of persistent pulmonary hypertension of the newborn"],"prefix":"10.1152","volume":"304","author":[{"given":"Cassidy","family":"Delaney","sequence":"first","affiliation":[{"name":"Pediatric Heart Lung Center, Sections of Neonatology and"},{"name":"Pulmonary Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Gien","sequence":"additional","affiliation":[{"name":"Pediatric Heart Lung Center, Sections of Neonatology 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