TY - JOUR T1 - The flavonoid quercetin reverses monocrotaline-induced pulmonary hypertension JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P2365 AU - Daniel Morales-Cano AU - Carmen Menendez AU - Javier Moral-Sanz AU - Bianca Barreira AU - Rosario Jimenez AU - Laura Moreno AU - Angel Cogolludo AU - Julio Cortijo AU - Juan Duarte AU - Franciso Perez-Vizcaino Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P2365.abstract N2 - 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, administration of quercetin for 10 days 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 phosphorylation. In vitro, quercetin induced pulmonary artery vasodilator effects, inhibited pulmonary artery smooth muscle cell proliferation and induced apoptosis. Conclusion: Quercetin reduced the mortality and the hemodynamic, vascular and cardiac anatomical changes induced by monocrotaline. The protective effect of quercetin against pulmonary hypertension involves both pulmonary arterial vasodilation and inhibition of smooth muscle cell proliferation. ER -