title: Quercetin and its metabolites inhibit the membrane NADPH oxidase activity in vascular smooth muscle cells from normotensive and spontaneously hypertensive rats.
abstract: Quercetin, the most abundant dietary flavonol, exerts antioxidant effects reducing vascular superoxide (O2(-)) and improving endothelial function in animal models of cardiovascular disease. Herein we evaluated the effects of quercetin, and its plasma metabolites, on the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase activity, the main source of O2(-) in the vessel wall, in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Quercetin and its metabolites isorhamnetin and kaempferol inhibited the NADPH-stimulated lucigenin-chemiluminescence signal in VSMCs from both strains. The inhibitory effect of quercetin-3-glucuronide increased after prolonged incubation and was inhibited in the presence of the β-glucuronidase inhibitor saccharolactone. These effects were unrelated to their O2(-) scavenging properties, since they induced only a small inhibition of the rate of pyrogallol autoxidation at high concentrations. All bioflavonoids tested acted as non-competitive inhibitors with respect to NADPH. In conclusion, quercetin and its metabolites inhibit the NADPH oxidase activity in VSMCs reducing O2(-) generation more efficiently than their effect as O2(-) scavengers. The effect of quercetin-3-glucuronide was due to deconjugation and release of free quercetin. The effect is similar in VSMCs from normotensive and hypertensive animals.
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Granada, Spain. jmduarte@ugr.es.
authors.forename: R
authors.initials: R
authors.lastname: Jimenez
authors.forename: R
authors.initials: R
authors.lastname: Lopez-Sepulveda
authors.forename: M
authors.initials: M
authors.lastname: Romero
authors.forename: M
authors.initials: M
authors.lastname: Toral
authors.forename: A
authors.initials: A
authors.lastname: Cogolludo
authors.forename: F
authors.initials: F
authors.lastname: Perez-Vizcaino
authors.forename: J
authors.initials: J
authors.lastname: Duarte
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D005966:Glucuronidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology; D044949:Kaempferols / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011794:Quercetin / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D000959:Antihypertensive Agents; D000975:Antioxidants; D006023:Glycoproteins; D044949:Kaempferols; C011473:beta-glucuronidase inhibitor; C443401:quercetin 3-O-glucuronide; C047368:3-methylquercetin; C006552:kaempferol; D011794:Quercetin; D019255:NADPH Oxidases; D005966:Glucuronidase