Protective effects of the flavonoid quercetin in chronic nitric oxide deficient rats.
OBJECTIVE
The present study analysed, for the first time, the effects of the flavonoid quercetin in rats after chronic inhibition of nitric oxide (NO) synthesis with Nomega-nitro-L-arginine methyl ester (L-NAME).


METHODS
Rats were divided randomly into five different treatment groups for 6 weeks: (1) vehicle (control, 1 ml of 1% methylcellulose once daily); (2) vehicle plus L-NAME (75 mg/100 ml in drinking water); (3) quercetin (10 mg/kg p.o. once daily); (4) quercetin (5 mg/kg p.o.) plus L-NAME; and (5) quercetin (10 mg/kg p.o.) plus L-NAME.


METHODS
The evolution of systolic blood pressure, morphological variables, proteinuria, plasma malondialdehyde and nitrite and nitrate concentrations, hepatic glutathione and malondialdehyde content, glutathione enzymes activity and vascular reactivity at the end of the experiment were analysed.


RESULTS
Quercetin markedly inhibited the development of L-NAME-induced hypertension. This effect was accompanied by a partial or full prevention of most of the effects induced by L-NAME, such as: (1) increases in the left ventricular and kidney weight indices; (2) proteinuria; (3) renal histological lesions, including hyaline arteriopathy and thickening of the vascular wall with moderate decrease of the lumen; (4) increased endothelium-dependent contraction; (5) increased vascular thromboxane B2 (TXB2) synthesis; (6) reduced plasma concentrations of nitrites plus nitrates (NOx); (7) increased plasma and hepatic malondialdehyde (MDA) concentrations; and (8) reduced glutathione peroxidase activity. In most cases these effects were dose dependent, but none of them were observed in normotensive animals.


CONCLUSIONS
This study confirms and extends the previous evidence about the antihypertensive effects and end-organ protection of the flavonoid quercetin in animal models of hypertension.
University of Granada, Department of Pharmacology, School of Pharmacy, Granada, Spain. jmduarte@ugr.es
Juan
J
Duarte
Rosario
R
Jiménez
Francisco
F
O'Valle
Milagros
M
Galisteo
Raquel
R
Pérez-Palencia
Felix
F
Vargas
Francisco
F
Pérez-Vizcaíno
Antonio
A
Zarzuelo
Juan
J
Tamargo
D000818:Animals; D001769:Blood / Q000378:metabolism; D001794:Blood Pressure; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D006352:Heart Ventricles; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009206:Myocardium / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000172:deficiency* / Q000378:metabolism; D009929:Organ Size; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011507:Proteinuria / Q000652:urine; D011794:Quercetin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014666:Vasomotor System / Q000503:physiopathology
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D008315:Malondialdehyde; D011794:Quercetin; D005979:Glutathione Peroxidase; D011451:Prostaglandin-Endoperoxide Synthases; D019331:NG-Nitroarginine Methyl Ester