Effect of tryptophan hydroxylase 1 deficiency on the development of hypoxia-induced pulmonary hypertension

Ian Morecroft, Yvonne Dempsie, Michael Bader, Diego J. Walther, Katarina Kotnik, Lynn Loughlin, Margaret Nilsen, Margaret R. MacLean*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

Tryptophan hydroxylase 1 catalyzes the rate-limiting step in the synthesis of serotonin in the periphery. Recently, it has been shown that expression of the tryptophan hydroxylase 1 gene is increased in lungs and pulmonary endothelial cells from patients with idiopathic pulmonary arterial hypertension. Here we investigated the effect of genetic deletion of tryptophan hydroxylase 1 on hypoxia-induced pulmonary arterial hypertension in mice by measuring pulmonary hemodynamics and pulmonary vascular remodeling before and after 2 weeks of hypoxia. In wild-type mice, hypoxia increased right ventricular pressure and pulmonary vascular remodeling. These effects of hypoxia were attenuated in the tryptophan hydroxylase 1mice. Hypoxia increased right ventricular hypertrophy in both wild-type and tryptophan hydroxylase 1mice suggesting that in vivo peripheral serotonin has a differential effect on the pulmonary vasculature and right ventricular hypertrophy. Contractile responses to serotonin were increased in pulmonary arteries from tryptophan hydroxylase 1mice. Hypoxia increased serotonin-mediated contraction in vessels from the wild-type mice, but this was not further increased by hypoxia in the tryptophan hydroxylase 1mice. In conclusion, these results indicate that tryptophan hydroxylase 1 and peripheral serotonin play an essential role in the development of hypoxia-induced elevations in pulmonary pressures and hypoxia-induced pulmonary vascular remodeling. In addition, the results suggest that, in mice, serotonin has differential effects on the pulmonary vasculature and right ventricular hypertrophy.

Original languageEnglish (US)
Pages (from-to)232-236
Number of pages5
JournalHypertension
Volume49
Issue number1
DOIs
StatePublished - Jan 2007

Keywords

  • Hypoxia
  • Pulmonary circulation
  • Serotonin
  • Transgenic animals

ASJC Scopus subject areas

  • Internal Medicine

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