Quercetin and Isorhamnetin Prevent Endothelial Dysfunction, Superoxide Production, and Overexpression of p47phox Induced by Angiotensin II in Rat Aorta

Abstract

The dietary flavonoid quercetin reduces blood pressure and improves endothelial function in several rat models of hypertension. We analyzed the effects of quercetin and its methylated metabolite isorhamnetin on the aortic endothelial dysfunction induced by incubation with angiotensin II (AngII) in vitro for 6 h. AngII diminished the relaxant responses to acetylcholine in phenylephrine-contracted aorta. Coincubation with quercetin or isorhamnetin, or addition of superoxide (O(2)(-)) dismutase or apocynin to the assay medium, prevented these inhibitory effects. At 6 h, AngII induced a marked increase in O(2)(-) production as measured by dihydroethidium fluorescence, which was prevented by quercetin and isorhamnetin. AngII also increased the expression of p47(phox), a regulatory subunit of the membrane NADPH oxidase. Immunohistochemical analysis revealed that overexpression of p47(phox) occurred mainly in the medial layer. p47(phox) overexpression was also prevented by quercetin and isorhamnetin. Taken together, these results show for the first time, to our knowledge, that quercetin and isorhamnetin prevent AngII-induced endothelial dysfunction by inhibiting the overexpression of p47(phox) and the subsequent increased O(2)(-) production, resulting in increased nitric oxide bioavailability.

Modulation of Nicotinamide Adenine Dinucleotide Phosphate Oxidase Expression and Function by 3′,4′-Dihydroxyflavonol in Phagocytic and Vascular Cells

“…Finally, we studied the effects of DiOHF on the expression of NADPH oxidase subunits because some recent studies have reported that flavonoids may modulate NADPH oxidase expression both in vitro and in vivo (Al-Awwadi et al, 2005;Sanchez et al, 2006Sanchez et al, , 2007. Interestingly, we found that DiOHF concentration dependently reduced the protein level of p47phox in differentiated HL-60 cells.…”

Redox Control of Renal Function and Hypertension

“…Further, treatment of phenylephrine-contracted aortic rings with Ang II resulted in decreased relaxation in response to ACh and increased O 2 Ϫ by dihydroethidium (DHE) staining. Treatment of these aortic rings with quercetin/isorhamnitin or SOD/apocynin decreased p47 phox expression and endothelial dysfunction (282).…”

Flavonoids fromInula britannicareduces oxidative stress through inhibiting expression and phosphorylation of p47phoxin VSMCs

“…The translocation of cytosolic p47 phox to the membrane is essential in the assembly process of this complex and plays a major role in NADPH oxidase activity in VSMCs (Touyz et al, 2003). The previous study has reported that quercetin prevent AngII-induced endothelial dysfunction by inhibiting the overexpression of p47 phox and the subsequent increased O 2˙− production in the medial layer of the vessel (Sanchez et al, 2007). Quercetin that is the main component of TFE, about 45%, as a member of the flavonoid family is widely discussed as an antioxidant.…”