Protective effects of the flavonoid quercetin in chronic nitric oxide deficient rats.

OBJECTIVES 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). DESIGN 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.