The Flavonoid Quercetin Reverses Pulmonary Hypertension in Rats Morales-Cano, Daniel Menéndez, Carmen Moreno, Enrique Moral-Sanz, Javier Barreira, Bianca Galindo Gallardo, Pilar Pandolfi, Rachele Jiménez, Rosario Moreno, Laura Cogolludo, Ángel Duarte Pérez, Juan Manuel Pérez-Vizcaíno, Francisco Pulmonary arteries Blood pressure Pulmonary hypertension Cell membranes Vasodilators Apoptosis Membrane potential Membrane staining Quercetin is a dietary flavonoid which exerts vasodilator, antiplatelet and antiproliferative effects and reduces blood pressure, oxidative status and end-organ damage in humans and animal models of systemic hypertension. We hypothesized that oral quercetin treatment might be protective in a rat model of pulmonary arterial hypertension. Three weeks after injection of monocrotaline, quercetin (10 mg/kg/d per os) or vehicle was administered for 10 days to adult Wistar rats. Quercetin significantly reduced mortality. In surviving animals, quercetin decreased pulmonary arterial pressure, right ventricular hypertrophy and muscularization of small pulmonary arteries. Classic biomarkers of pulmonary arterial hypertension such as the downregulated expression of lung BMPR2, Kv1.5, Kv2.1, upregulated survivin, endothelial dysfunction and hyperresponsiveness to 5-HT were unaffected by quercetin. Quercetin significantly restored the decrease in Kv currents, the upregulation of 5-HT2A receptors and reduced the Akt and S6 phosphorylation. In vitro, quercetin induced pulmonary artery vasodilator effects, inhibited pulmonary artery smooth muscle cell proliferation and induced apoptosis. In conclusion, quercetin is partially protective in this rat model of PAH. It delayed mortality by lowering PAP, RVH and vascular remodeling. Quercetin exerted effective vasodilator effects in isolated PA, inhibited cell proliferation and induced apoptosis in PASMCs. These effects were associated with decreased 5-HT2A receptor expression and Akt and S6 phosphorylation and partially restored Kv currents. Therefore, quercetin could be useful in the treatment of PAH. 2015-02-19T14:02:00Z 2015-02-19T14:02:00Z 2014 info:eu-repo/semantics/article Morales-Cano, D.; et al. The Flavonoid Quercetin Reverses Pulmonary Hypertension in Rats. Plos One, 9(12): e114492 (2014). [http://hdl.handle.net/10481/34881] 1932-6203 http://hdl.handle.net/10481/34881 10.1371/journal.pone.0114492 eng http://creativecommons.org/licenses/by-nc-nd/3.0/ info:eu-repo/semantics/openAccess Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License Public Library of Science (PLOS)