Glucuronidated Quercetin Lowers Blood Pressure in Spontaneously Hypertensive Rats via Deconjugation
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AutorGalindo Gallardo, Pilar; Rodríguez Gómez, Isabel; González-Manzano, Susana; Dueñas, Montserrat; Jiménez Moleón, Rosario; Menéndez, Carmen; Vargas, Félix; Tamargo, Juan; Santos-Buelga, Celestino; Pérez-Vizcaíno, Francisco; Duarte Pérez, Juan Manuel
Public Library of Science (PLOS)
AntihypertensivesBlood plasmaBlood pressureDrug metabolismHeart rateHypertensionMesenteric arteriesMethylation
Galindo, P.; et al. Glucuronidated Quercetin Lowers Blood Pressure in Spontaneously Hypertensive Rats via Deconjugation. Plos One, 7(3): e32673 (2012). [http://hdl.handle.net/10481/31055]
PatrocinadorThis work was supported by Grants from the Spanish Ministerio de Ciencia e Innovación (AGL2007-66108, SAF2008-03948, AGL2009-12001 and SAF2010-22066) and Consolider-Ingenio 2010 Programme (CSD2007-00063), Junta de Andalucia (Proyecto de Excelencia P06-CTS-01555), and Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (Red HERACLES RD06/0009 and Red de Investigación Renal, REDinREN RD06/0016/0017).
[Background] Chronic oral quercetin reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (aglycone) is usually not present in plasma, because it is rapidly metabolized into conjugated, mostly inactive, metabolites. The aim of the study is to analyze whether deconjugation of these metabolites is involved in the blood pressure lowering effect of quercetin. [Methodology/Principal Findings] We have analyzed the effects on blood pressure and vascular function in vitro of the conjugated metabolites of quercetin (quercetin-3-glucuronide, Q3GA; isorhamnetin-3-glucuronide, I3GA; and quercetin-3′-sulfate, Q3'S) in spontaneously hypertensive rats (SHR). Q3GA and I3GA (1 mg/kg i.v.), but not Q3'S, progressively reduced mean blood pressure (MBP), measured in conscious SHR. The hypotensive effect of Q3GA was abolished in SHR treated with the specific inhibitor of β-glucuronidase, saccharic acid 1,4-lactone (SAL, 10 mg/ml). In mesenteric arteries, unlike quercetin, Q3GA had no inhibitory effect in the contractile response to phenylephrine after 30 min of incubation. However, after 1 hour of incubation Q3GA strongly reduced this contractile response and this effect was prevented by SAL. Oral administration of quercetin (10 mg/Kg) induced a progressive decrease in MBP, which was also suppressed by SAL. [Conclusions] Conjugated metabolites are involved in the in vivo antihypertensive effect of quercetin, acting as molecules for the plasmatic transport of quercetin to the target tissues. Quercetin released from its glucuronidated metabolites could be responsible for its vasorelaxant and hypotensive effect.