Quercetin and isorhamnetin prevent endothelial dysfunction, superoxide production, and overexpression of p47phox induced by angiotensin II in rat aorta.
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.
Sanchez
Manuel
M
Department of Pharmacology, School of Pharmacy, Universidad de Granada, 18071 Granada, Spain.
Lodi
Federica
F
Vera
Rocio
R
Villar
Inmaculada C
IC
Cogolludo
Angel
A
Jimenez
Rosario
R
Moreno
Laura
L
Romero
Miguel
M
Tamargo
Juan
J
Perez-Vizcaino
Francisco
F
Duarte
Juan
J
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D044948:Flavonols / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology* / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014018:Tissue Distribution; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D044948:Flavonols; D047495:PPAR gamma; D014662:Vasoconstrictor Agents; C047368:3-methylquercetin; D013481:Superoxides; D000804:Angiotensin II; D011794:Quercetin; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1