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

Item Type:Article
Title:Effect of tryptophan hydroxylase 1 deficiency on the development of hypoxia-induced pulmonary hypertension
Creators Name:Morecroft, I. and Dempsie, Y. and Bader, M. and Walther, D.J. and Kotnik, K. and Loughlin, L. and Nilsen, M. and Maclean, M.R.
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 1(-/-) mice. Hypoxia increased right ventricular hypertrophy in both wild-type and tryptophan hydroxylase 1(-/-)mice 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 1(-/-) mice. Hypoxia increased serotonin-mediated contraction in vessels from the wild-type mice, but this was not further increased by hypoxia in the tryptophan hydroxylase 1(-/-) mice. 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.
Keywords:Pulmonary Circulation, Serotonin, Hypoxia, Transgenic Animals, Animals, Mice
Source:Hypertension
ISSN:0194-911X
Publisher:American Heart Association (U.S.A.)
Volume:49
Number:1
Page Range:232-236
Date:January 2007
Official Publication:https://doi.org/10.1161/01.HYP.0000252210.58849.78
PubMed:View item in PubMed

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