C. Oakley, E. Wouters, M. Aubier, G. Simonneau, and B. Begaud, Appetite-suppressant 347 drugs and the risk of primary pulmonary hypertension. International Primary Pulmonary 348

J. Alvarez, M. Sanceaume, C. Advenier, and O. Spreux-varoquaux, Differential 350 changes in brain and platelet 5-HT concentrations after steady-state achievement and 351 repeated administration of antidepressant drugs in mice, Eur Neuropsychopharmacol, vol.10, issue.3, pp.352-383, 1999.

F. Cote, E. Thevenot, C. Fligny, Y. Fromes, M. Darmon et al., Disruption of the nonneuronal tph1 gene demonstrates the importance of peripheral serotonin in cardiac function, Proceedings of the National Academy of Sciences, vol.100, issue.23, pp.13525-13530, 2003.
DOI : 10.1073/pnas.2233056100

M. Darmon, B. Guibert, V. Leviel, M. Ehret, M. Maitre et al., Sequence of Two mRNAs Encoding Active Rat Tryptophan Hydroxylase, Journal of Neurochemistry, vol.2, issue.1, pp.312-316, 1988.
DOI : 10.1073/pnas.82.4.1074

M. Humbert, G. Simonneau, N. Hanoun, F. Saurini, M. Hamon et al., Cross talk 364 between endothelial and smooth muscle cells in pulmonary hypertension: critical role for 365 serotonin-induced smooth muscle hyperplasia, Circulation, vol.113, pp.1857-1864, 2006.

P. Dartevelle, M. Hamon, and S. Adnot, Serotonin transporter overexpression is 371 responsible for pulmonary artery smooth muscle hyperplasia in primary pulmonary 372 hypertension, J Clin Invest, vol.108, issue.9, pp.1141-1150, 2001.

B. Fanburg and S. Lee, A new role for an old molecule: serotonin as a mitogen, Am J, p.374

H. Farber and J. Loscalzo, Pulmonary Arterial Hypertension, New England Journal of Medicine, vol.351, issue.16, pp.1655-376, 2004.
DOI : 10.1056/NEJMra035488

M. Gershon, Review article: roles played by 5-hydroxytryptamine in the physiology of the bowel, Alimentary Pharmacology & Therapeutics, vol.28, issue.3, pp.15-30, 1999.
DOI : 10.1046/j.1365-2036.1999.00002.x-i2

D. Rodman, M. Hamon, S. Adnot, and S. Eddahibi, Transgenic mice overexpressing the 385 5-hydroxytryptamine transporter gene in smooth muscle develop pulmonary hypertension, p.386

S. Adnot and S. Eddahibi, Serotonin transporter inhibition prevents and reverses 389

E. Eddahibi and S. , Dichloroacetate treatment partially regresses established pulmonary 393 hypertension in mice with SM22alpha-targeted overexpression of the serotonin 394 transporter, FASEB J, vol.23, issue.395, pp.4135-4147, 2009.

M. Hamon, C. Fattaccini, A. J. Gallissot, M. Martin, P. Gozlan et al., Alterations 396 in central serotonin and dopamine turnover in rats treated with ipsapirone and other 5- 397 hydroxytryptamine1A agonists with potential anxiolytic properties, J Pharmacol Exp, p.398

P. Poubeau, J. Cerrina, P. Duroux, and L. Drouet, Increased plasma serotonin in primary 401 pulmonary hypertension, Am J Med, vol.99, issue.402, pp.249-254, 1995.

M. Hamon and S. Adnot, Tryptophan hydroxylase 1 knockout and tryptophan 404

L. Drouet, M. Humbert, G. Simonneau, and L. Maroteaux, Function of the serotonin 5- 408 hydroxytryptamine 2B receptor in pulmonary hypertension, Nat Med, vol.8, issue.20, pp.1129-1135, 2002.

S. Lee, W. Wang, and F. Bl, Superoxide as an Intermediate Signal for Serotonin-Induced Mitogenesis 11This study was supported by Research Grant HL 32723 from the Heart, Lung, and Blood Institute of the National Institutes of Health., Free Radical Biology and Medicine, vol.24, issue.5, pp.855-858, 1998.
DOI : 10.1016/S0891-5849(97)00359-6

S. Lee, W. Wang, B. Moore, and F. Bl, Dual effect of serotonin on growth of bovine pulmonary artery smooth muscle cells in culture, Circulation Research, vol.68, issue.5, pp.1362-1368, 1991.
DOI : 10.1161/01.RES.68.5.1362

M. Maclean, G. Sweeney, M. Baird, K. Mcculloch, M. Houslay et al., 5-Hydroxytryptamine receptors mediating vasoconstriction in pulmonary arteries from control and pulmonary hypertensive rats, British Journal of Pharmacology, vol.267, issue.Suppl. 7, pp.917-930, 1996.
DOI : 10.1111/j.1476-5381.1996.tb15760.x

M. Maclean, Effect of tryptophan hydroxylase 1 deficiency on the development of 427 hypoxia-induced pulmonary hypertension, Hypertension, vol.49, issue.428, pp.232-236, 2007.

K. Stenmark, P. Thistlethwaite, N. Weissmann, J. Yuan, and E. Weir, Cellular 430 and molecular basis of pulmonary arterial hypertension, J Am Coll Cardiol, vol.54, issue.432, pp.20-31, 2009.

K. Sato, S. Webb, A. Tucker, M. Rabinovitch, O. Brien et al., Factors Influencing the Idiopathic Development of Pulmonary Hypertension in the Fawn Hooded Rat, American Review of Respiratory Disease, vol.145, issue.4_pt_1, pp.793-797, 1992.
DOI : 10.1164/ajrccm/145.4_Pt_1.793

*. and *. P<0, 001 compared with corresponding values in vehicle-treated SM22-5- 468 HTT+ mice, #P<0.05 for the intergroup comparison

L. Tph-inhibitor, 5-HTT inhibitor citalopram, both, or 480 vehicle, (D) Number of proliferating vascular cells expressed as the percentage of Ki67-labelled 481

. E. Values-are-means±s, 05, **P<0.01, and ***P<0.001 compared with corresponding 485 values in vehicle-treated hypoxic mice

*. and *. P<0, 001 compared with corresponding values in vehicle-treated mice, ##P<0.01, and ###P<0.001 for the intergroup comparison

R. Lv+s, 02***# § Values are means ± S.E.M. of 6 independent determinations in each group; RV, right ventricle; LV, left ventricle, and ***P<0.001 vs respective values in vehicle-treated SM22-5-HTT+ mice. #P<0.05 for comparison with LP533401 treatment alone; §P<0.05 for comparison with Citalopram treatment alone

±. S. Values-are-means, of 6 independent determinations in each group; RV, right ventricle; LV, left ventricle. *p <.05 vs respective values in vehicle-treated hypoxic mice Normoxic Hypoxic Control LP533401 Vehicle LP533401 Citalopram Combination Body Weight, g 27, * Heart Rate