Endothelium-Independent Vasodilator Effects of the Flavonoid Quercetin and Its Methylated Metabolites in Rat Conductance and Resistance Arteries

Abstract

The flavonoid quercetin is metabolized into isorhamnetin, tamarixetin, and kaempferol, the vascular effects of which are unknown. In the present study, the effects of quercetin and its metabolites were analyzed on isometric tension in isolated rat thoracic and abdominal aorta, in isolated intact and ␤-escinpermeabilized iliac arteries, and on perfusion pressure in the isolated mesenteric resistance vascular bed. In noradrenalineprecontracted vessels, the four flavonoids produced a vasodilator effect, which was inversely correlated with the diameter of the vessel studied; i.e., quercetin, isorhamnetin, tamarixetin, and kaempferol were 5-, 25-, 4-, and 6-fold, respectively, more potent in the resistance mesenteric bed (Ϫlog IC 50 ϭ 5.35 Ϯ 0.15, 5.89 Ϯ 0.11, 5.34 Ϯ 0.10, and 5.66 Ϯ 0.06, respectively) than in the thoracic aorta (Ϫlog IC 50 ϭ 4.68 Ϯ 0.08, 4.61 Ϯ 0.08, 4.73 Ϯ 0.11, and 4.81 Ϯ 0.13, respectively; n ϭ 4 -6). The vasodilator responses of quercetin and isorhamnetin were not significantly modified after removal of the endothelium in the thoracic aorta or in the mesenteric bed. Furthermore, the guanylate cyclase inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one; 10 Ϫ6 M), the adenylate cyclase inhibitor SQ22536 [9-(tetrahydro-2-furanyl)-9H-purin-6-amine; 10Ϫ6 M], KCl (40 mM), or ouabain (10 Ϫ3 M) had no effect on isorhamnetin-induced vasodilation in the mesenteric bed. In permeabilized iliac arteries stimulated with Ca 2ϩ (pCa of 5.9), isorhamnetin was also significantly more potent (Ϫlog IC 50 ϭ 5.27 Ϯ 0.15) than quercetin (Ϫlog IC 50 ϭ 4.56 Ϯ 0.15). In conclusion, quercetin and its metabolites showed vasodilator effects with selectivity toward the resistance vessels. These effects are not due to or modulated by endothelial factors and are unrelated to changes in cytosolic Ca 2ϩ .Flavonoids comprise a large group of secondary metabolites widely distributed throughout the plant kingdom, including food plants. The daily flavonoid intake in the human diet (mainly from onions, apples, grapes, wine, tea, berries, herbs, and spices) is highly variable, with estimations ranging from 23 mg (flavonols plus flavones; Hertog et al., 1993b) to more than 500 mg (total flavonoids;

On the vasoprotective mechanisms underlying novel β-phosphorylated nitrones: Focus on free radical characterization, scavenging and NO-donation in a biological model of oxidative stress

“…-scavenging properties (Table 4) which preserves endothelium-derived NO biodisponibility. This second chemical mechanism by which PPNs may improve vasorelaxant response to SNP agrees with previous observations in vessels treated with polyphenolic compounds such as quercetin, which strongly enhanced vasodilatation in an endotheliumindependent manner [58,59].…”

Biphasic effect of Psidium guajava Linn. (Myrtaceae) leaf aqueous extract on rat isolated vascular smooth muscles

“…Previous studies in our laboratories and elsewhere have shown that quercetin, kaempherol, morin, myricetin, luteolin and rutin, all present in PGE, possess vasodilator effects in rat isolated aorta and porcine coronary artery (Duarte et al, 1993a, b;Herrera et al, 1996;Perez-Vizcaíno et al, 2002;Ajay et al, 2003;Xu et al, 2007). In the present study, we report for the first time in biomedical literature, that Psidium guajava crude leaf aqueous extract, which contains many flavonoids, especially quercetin, induces vascular smooth muscle relaxation, with potency lower than that of pure quercetin (Chiwororo and Ojewole, 2008 -unpublished observation).…”

“…Quercetin is a potent antioxidant, and has been shown to protect nitric oxide from scavenging actions of superoxide anion (Ajay et al, 2006). In some reports, the vasorelaxation induced by quercetin (and other related flavonoids) was endothelium-independent (Duarte et al, 1993a, Perez-Vizcaíno et al, 2002, or very weakly (less than 2-fold shift) inhibited by endothelial removal (Chen and Pace-Asciak, 1996). However, in a chronic study by Duarte et al (2001), quercetin restored endothelium-dependent relaxation.…”

Physicochemical characteristics of rapidly dried onion powder and its anti-atherogenic effect on rats fed high-fat diet

“…According to Williamson & Manach (2005), quercetin has a relatively long plasma half-life of 11-28 h, and a 50 mg dose would lead to concentrations of up to ~0.75-1.5 µmol/L in plasma. This plasma concentration may be effective for vascular protection because significant vasodilator responses were observed in the mesenteric bed at concentration of flavonoids (quercetin and its metabolites) of 0.3-3.0 µmol/L (Pérez-Vizcaíno et al, 2002). Concerning this, 12.0 g of OP can provide 50 mg of total quercetin and may increase plasma concentration of flavonoids up to the meaningful level.…”