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Biochemical, Molecular, and Genetic Mechanisms

Quercetin and Isorhamnetin Prevent Endothelial Dysfunction, Superoxide Production, and Overexpression of p47^phox Induced by Angiotensin II in Rat Aorta¹

² Department of Pharmacology, School of Pharmacy, Universidad de Granada, 18071 Granada, Spain and ³ Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain

^* To whom correspondence should be addressed. E-mail: fperez{at}med.ucm.es.

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 (O₂^–) dismutase or apocynin to the assay medium, prevented these inhibitory effects. At 6 h, AngII induced a marked increase in O₂^– 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 O₂^– production, resulting in increased nitric oxide bioavailability.

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