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| Item Type: | Article |
|---|---|
| Title: | Effect of tryptophan hydroxylase 1 deficiency on the development of hypoxia-induced pulmonary hypertension |
| Creators Name: | Morecroft, I., Dempsie, Y., Bader, M., Walther, D.J., Kotnik, K., Loughlin, L., 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 |
| 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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