title: Different cardiovascular protective effects of quercetin administered orally or intraperitoneally in spontaneously hypertensive rats.
abstract: We tested whether the administration procedure of quercetin affects its metabolite profile and antihypertensive activity. Spontaneously hypertensive rats (SHR) were randomly assigned to four experimental treatments: (1) 1 mL of 1% methylcellulose by oral gavage and 2% DMSO i.p. (control group); (2) 10 mg kg⁻¹ quercetin by oral gavage once daily and 2% DMSO i.p.; (3) 10 mg kg⁻¹ quercetin by oral gavage divided in two daily doses (5 + 5 at 12 h intervals) and 2% DMSO i.p.; (4) 1 mL of 1% methylcellulose by oral gavage and 10 mg kg⁻¹ quercetin i.p. injection. Rats were treated daily for 5 weeks. Single dose and two daily doses, in a long-term oral treatment were equally efficient, both restoring the impaired aortic endothelium-dependent vasodilatation and reducing mesenteric contractile response to phenylephrine, systolic blood pressure, heart rate, and heart and kidney hypertrophy. Attenuation of vascular NADPH oxidase-driven O₂⁻ production was also found in orally treated rats. Intraperitoneal administration reduced, to lesser extent than oral administration, the increased systolic blood pressure, being without effect to the endothelial dysfunction and vascular oxidative stress. In contrast, greater levels of metabolites were quantified following intraperitoneal compared to oral administration at any time point, except for higher plasma methylated quercetin aglycone in oral as compared to intraperitoneal administration at 2 but not at 8 h. In conclusion, oral quercetin was superior to intraperitoneal administration for the protection from cardiovascular complications in SHR. No differences were found between the oral administration as a single daily dose or divided into two daily doses.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Universidad de Granada, 18071 Granada, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Galindo
authors.forename: S
authors.initials: S
authors.lastname: González-Manzano
authors.forename: M J
authors.initials: MJ
authors.lastname: Zarzuelo
authors.forename: M
authors.initials: M
authors.lastname: Gómez-Guzmán
authors.forename: A M
authors.initials: AM
authors.lastname: Quintela
authors.forename: A
authors.initials: A
authors.lastname: González-Paramás
authors.forename: C
authors.initials: C
authors.lastname: Santos-Buelga
authors.forename: F
authors.initials: F
authors.lastname: Pérez-Vizcaíno
authors.forename: J
authors.initials: J
authors.lastname: Duarte
authors.forename: R
authors.initials: R
authors.lastname: Jiménez
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015870:Gene Expression; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D008297:Male; D020011:Protective Agents / Q000008:administration & dosage* / Q000378:metabolism; D011794:Quercetin / Q000008:administration & dosage* / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D000959:Antihypertensive Agents; D020011:Protective Agents; D011794:Quercetin