title: Glucuronidated quercetin lowers blood pressure in spontaneously hypertensive rats via deconjugation.
abstract: 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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Granada, Granada, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Galindo
authors.forename: Isabel
authors.initials: I
authors.lastname: Rodriguez-Gómez
authors.forename: Susana
authors.initials: S
authors.lastname: González-Manzano
authors.forename: Montserrat
authors.initials: M
authors.lastname: Dueñas
authors.forename: Rosario
authors.initials: R
authors.lastname: Jiménez
authors.forename: Carmen
authors.initials: C
authors.lastname: Menéndez
authors.forename: Félix
authors.initials: F
authors.lastname: Vargas
authors.forename: Juan
authors.initials: J
authors.lastname: Tamargo
authors.forename: Celestino
authors.initials: C
authors.lastname: Santos-Buelga
authors.forename: Francisco
authors.initials: F
authors.lastname: Pérez-Vizcaíno
authors.forename: Juan
authors.initials: J
authors.lastname: Duarte
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D005937:Glucaric Acid / Q000494:pharmacology; D005966:Glucuronidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology; D008297:Male; D050217:Metabolic Detoxication, Phase II / Q000502:physiology*; D015394:Molecular Structure; D011794:Quercetin / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D014664:Vasodilation / Q000187:drug effects*
chemical_list: C571832:D-Glucaric acid, 1,4-lactone; D007783:Lactones; D011794:Quercetin; D005966:Glucuronidase; D005937:Glucaric Acid