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.

Activation of Kv7 channels as a novel mechanism for NO/cGMP‐induced pulmonary vasodilation

“…The higher concentrations reported to induce this effect, the mechanism involved (S‐nitrosylation) and the possible K v 7 channel subtypes targeted may explain the differences with respect to our study. Among the different K v 7 channels expressed in vascular smooth muscle (Morales‐Cano et al, , ; Yeung et al, ) including the pulmonary circulation (Joshi et al, ; Morales‐Cano et al, ), Kv7.4 and K v 7.5 channels are considered to play a predominant role in regulating vascular tone (Barrese et al, ). A previous study (Stott et al, ) showed that K v 7.4 currents are increased following the application of cGMP in HEK‐293 cells.…”

Effects of Quercetin on Blood Pressure: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

“…Its positive effect on hypertension was documented for the first time on spontaneously hypertensive rats, in an experimental model that mimics human hypertension . Since then, many experimental and human studies showed that quercetin exerts vasodilator, antiplatelet, and antiproliferative effects, decreasing oxidative status, blood pressure (BP), and end‐organ damage . The BP‐lowering effect of quercetin is more evident in subjects with certain comorbidities such as metabolic syndrome or in smokers .…”

“…19 Since then, many experimental and human studies showed that quercetin exerts vasodilator, antiplatelet, and antiproliferative effects, decreasing oxidative status, blood pressure (BP), and endorgan damage. [20][21][22][23][24] The BP-lowering effect of quercetin is more evident in subjects with certain comorbidities such as metabolic syndrome or in smokers. 25 Different studies tried to establish a connection between the antihypertensive effect of quercetin and certain phenotypes such as the apolipoproteins (apo) E3 and E4, but so far results are conflicting.…”

Effects of phyto‐oestrogen quercetin on productive performance, hormones, reproductive organs and apoptotic genes in laying hens

“…Quercetin (3,3′,4′,5,7‐pentahydroxyflavone) is one of the main dietary flavonoids, which is found in a variety of beverages, fruits and vegetables, known as a phyto‐oestrogen (Lamson & Brignall, ). Studies showed that quercetin has several bioactivities, including improving intestinal environment, antioxidant, anti‐apoptotic properties (Johinke, De, & Bathgate, ; Morales‐Cano et al., ; Romero et al., ), etc. Previous studies indicated that quercetin increased egg production and feed efficiency in laying hens (Liu et al., , ).…”

“…Studies showed that quercetin has several bioactivities, including improving intestinal environment, antioxidant, anti-apoptotic properties (Johinke, De, & Bathgate, 2014;Morales-Cano et al, 2014;Romero et al, 2009), etc. Previous studies indicated that quercetin increased egg production and feed efficiency in laying hens (Liu et al, 2013(Liu et al, , 2014.…”