In vivo effects of a combined 5-HT1B receptor/SERT antagonist in experimental pulmonary hypertension

Ian Morecroft, Louisa Pang, Marta Baranowska, Margaret Nilsen, Lynn Loughlin, Yvonne Dempsie, Caroline Millet, Margaret R MacLean

Research output: Contribution to journalArticle

Abstract

A mechanism for co-operation between the serotonin (5-hydroxytryptamine, 5-HT) transporter and 5-HT1B receptor in mediating pulmonary artery vasoconstriction and proliferation of pulmonary artery smooth muscle cells has been demonstrated in vitro. Here we determine, for the first time, the in vivo effects of a combined 5-HT1B receptor/serotonin transporter antagonist (LY393558) with respect to the development of pulmonary arterial hypertension (PAH) and its in vitro effects in human pulmonary artery smooth muscle cells (hPASMCs) derived from idiopathic PAH (IPAH) patients. We determined the effects of LY393558 as well as a selective serotonin transporter inhibitor, citalopram, on right ventricular pressure, right ventricular hypertrophy, and pulmonary vascular remodelling in wildtype mice and mice over-expressing serotonin transporter (SERT+ mice) before and after hypoxic exposure. We also compared their effectiveness at reversing PAH in SERT+ mice and hypoxic mice. Further, we examined the proliferative response to serotonin in IPAH hPASMCs. We also clarified the pharmacology of serotonin-induced vasoconstriction and 5-HT1B receptor/serotonin transporter interactions in mouse isolated pulmonary artery.
Original languageEnglish
Pages (from-to)593-603
Number of pages11
JournalCardiovascular Research
Volume85
Issue number3
DOIs
Publication statusPublished - 2010

Keywords

  • serotonin transporter
  • pulmonary arterial hypertension
  • smooth muscle cells

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    Morecroft, I., Pang, L., Baranowska, M., Nilsen, M., Loughlin, L., Dempsie, Y., Millet, C., & MacLean, M. R. (2010). In vivo effects of a combined 5-HT1B receptor/SERT antagonist in experimental pulmonary hypertension. Cardiovascular Research, 85(3), 593-603. https://doi.org/10.1093/cvr/cvp306