title: The flavonoid quercetin reverses pulmonary hypertension in rats.
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.
authors.affiliation: Department of Pharmacology, School of Medicine, University Complutense of Madrid, Madrid, Spain; Ciber Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Morales-Cano
authors.affiliation: Department of Pharmacology, School of Medicine, University Complutense of Madrid, Madrid, Spain; Ciber Enfermedades Respiratorias (CIBERES), Madrid, Spain; Faculty of Health Sciences, Universidad Autónoma de Chile, Santiago, Chile.
authors.forename: Carmen
authors.initials: C
authors.lastname: Menendez
authors.affiliation: Department of Pharmacology, School of Medicine, University Complutense of Madrid, Madrid, Spain; Ciber Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Moreno
authors.affiliation: Department of Pharmacology, School of Medicine, University Complutense of Madrid, Madrid, Spain; Ciber Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Moral-Sanz
authors.affiliation: Department of Pharmacology, School of Medicine, University Complutense of Madrid, Madrid, Spain; Ciber Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Bianca
authors.initials: B
authors.lastname: Barreira
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Granada, Granada, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Galindo
authors.affiliation: Department of Pharmacology, School of Medicine, University Complutense of Madrid, Madrid, Spain; Ciber Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Rachele
authors.initials: R
authors.lastname: Pandolfi
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Granada, Granada, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Jimenez
authors.affiliation: Department of Pharmacology, School of Medicine, University Complutense of Madrid, Madrid, Spain; Ciber Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Moreno
authors.affiliation: Department of Pharmacology, School of Medicine, University Complutense of Madrid, Madrid, Spain; Ciber Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Cogolludo
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Granada, Granada, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Duarte
authors.affiliation: Department of Pharmacology, School of Medicine, University Complutense of Madrid, Madrid, Spain; Ciber Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Perez-Vizcaino
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000235:genetics; D017380:Hypertrophy, Right Ventricular / Q000503:physiopathology; D008297:Male; D008564:Membrane Potentials; D011794:Quercetin / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D016019:Survival Analysis
chemical_list: D011794:Quercetin