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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/34881

Title: The Flavonoid Quercetin Reverses Pulmonary Hypertension in Rats
Authors: 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
Issue Date: 2014
Abstract: 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.
Sponsorship: This work was supported by grants and fellowships by the Spanish Ministerio de Economia y Competitividad (SAF2011-28150 to F.P-V, SAF2010-22066-C02-01 to JD, and −02 to AC); Instituto de Salud Carlos III Red HERACLES RD06/0009 to JD; Miguel Servet Program CP12/03304 to LM; predoctoral grants BES-2012-051904 to DMS, CM, JMS, and PG; and Junta de Andalucia (Proyecto de excelencia, P12-CTS-2722).
Publisher: Public Library of Science (PLOS)
Keywords: Pulmonary arteries
Blood pressure
Pulmonary hypertension
Cell membranes
Vasodilators
Apoptosis
Membrane potential
Membrane staining
URI: http://hdl.handle.net/10481/34881
ISSN: 1932-6203
Rights : Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License
Citation: 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]
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