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The flavonoid quercetin reverses pulmonary hypertension in rats.

Morales-Cano D, Menendez C, Moreno E, Moral-Sanz J, Barreira B, Galindo P, Pandolfi R, Jimenez R, Moreno L, Cogolludo A, Duarte J, Perez-Vizcaino F - PLoS ONE (2014)

Bottom Line: Quercetin significantly reduced mortality.Quercetin significantly restored the decrease in Kv currents, the upregulation of 5-HT2A receptors and reduced the Akt and S6 phosphorylation.These effects were associated with decreased 5-HT2A receptor expression and Akt and S6 phosphorylation and partially restored Kv currents.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, School of Medicine, University Complutense of Madrid, Madrid, Spain; Ciber Enfermedades Respiratorias (CIBERES), Madrid, Spain.

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.

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Related in: MedlinePlus

Quercetin (Quer) does not prevent vascular dysfunction.(A) Relaxant effects of pulmonary arteries to the endothelium-dependent vasodilator acetylcholine in pulmonary arteries stimulated with phenylephrine. (B) Expression of eNOS mRNA in pulmonary arteries homogenates analyzed by RT-PCR. (C) Contractile responses to 5-HT in pulmonary arteries expressed as a percent of a previous response to KCl. Results are means ± SEM of 4–9 experiments. Results are means ± SEM of 4–8 animals normalized by the expression of β-actin. * indicates P<0.05 versus monocrotaline (MCT), # and ## P<0.05 and P<0.01 versus control (Ctrl).
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pone-0114492-g007: Quercetin (Quer) does not prevent vascular dysfunction.(A) Relaxant effects of pulmonary arteries to the endothelium-dependent vasodilator acetylcholine in pulmonary arteries stimulated with phenylephrine. (B) Expression of eNOS mRNA in pulmonary arteries homogenates analyzed by RT-PCR. (C) Contractile responses to 5-HT in pulmonary arteries expressed as a percent of a previous response to KCl. Results are means ± SEM of 4–9 experiments. Results are means ± SEM of 4–8 animals normalized by the expression of β-actin. * indicates P<0.05 versus monocrotaline (MCT), # and ## P<0.05 and P<0.01 versus control (Ctrl).

Mentions: Monocrotaline significantly decreased the maximal relaxation evoked by acetylcholine in isolated rat pulmonary arteries (Figure 7A) and no changes were found in rats treated with quercetin. The endothelial dysfunction was accompanied by a reduction in the expression of eNOS which again was not reverted by quercetin (Figure 7B). Monocrotaline also produced a significant hyperresponsiveness of pulmonary arteries to 5-HT (Emax values of 102±3% of the response to KCl vs 35±1% in control) and quercetin again was not able to prevent it (98±1%) (Figure 7C).


The flavonoid quercetin reverses pulmonary hypertension in rats.

Morales-Cano D, Menendez C, Moreno E, Moral-Sanz J, Barreira B, Galindo P, Pandolfi R, Jimenez R, Moreno L, Cogolludo A, Duarte J, Perez-Vizcaino F - PLoS ONE (2014)

Quercetin (Quer) does not prevent vascular dysfunction.(A) Relaxant effects of pulmonary arteries to the endothelium-dependent vasodilator acetylcholine in pulmonary arteries stimulated with phenylephrine. (B) Expression of eNOS mRNA in pulmonary arteries homogenates analyzed by RT-PCR. (C) Contractile responses to 5-HT in pulmonary arteries expressed as a percent of a previous response to KCl. Results are means ± SEM of 4–9 experiments. Results are means ± SEM of 4–8 animals normalized by the expression of β-actin. * indicates P<0.05 versus monocrotaline (MCT), # and ## P<0.05 and P<0.01 versus control (Ctrl).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4252144&req=5

pone-0114492-g007: Quercetin (Quer) does not prevent vascular dysfunction.(A) Relaxant effects of pulmonary arteries to the endothelium-dependent vasodilator acetylcholine in pulmonary arteries stimulated with phenylephrine. (B) Expression of eNOS mRNA in pulmonary arteries homogenates analyzed by RT-PCR. (C) Contractile responses to 5-HT in pulmonary arteries expressed as a percent of a previous response to KCl. Results are means ± SEM of 4–9 experiments. Results are means ± SEM of 4–8 animals normalized by the expression of β-actin. * indicates P<0.05 versus monocrotaline (MCT), # and ## P<0.05 and P<0.01 versus control (Ctrl).
Mentions: Monocrotaline significantly decreased the maximal relaxation evoked by acetylcholine in isolated rat pulmonary arteries (Figure 7A) and no changes were found in rats treated with quercetin. The endothelial dysfunction was accompanied by a reduction in the expression of eNOS which again was not reverted by quercetin (Figure 7B). Monocrotaline also produced a significant hyperresponsiveness of pulmonary arteries to 5-HT (Emax values of 102±3% of the response to KCl vs 35±1% in control) and quercetin again was not able to prevent it (98±1%) (Figure 7C).

Bottom Line: Quercetin significantly reduced mortality.Quercetin significantly restored the decrease in Kv currents, the upregulation of 5-HT2A receptors and reduced the Akt and S6 phosphorylation.These effects were associated with decreased 5-HT2A receptor expression and Akt and S6 phosphorylation and partially restored Kv currents.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, School of Medicine, University Complutense of Madrid, Madrid, Spain; Ciber Enfermedades Respiratorias (CIBERES), Madrid, Spain.

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.

Show MeSH
Related in: MedlinePlus