Glucosyl hesperidin (G-hesperidin) is a water-soluble derivative of hesperidin. In the present study, the short-term effects of G-hesperidin and hesperetin, a putative metabolite of G-hesperidin, in spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto rats (WKY) were investigated. Single oral administration of G-hesperidin (10 to 50 mg/kg) induced a dose-dependent reduction in systolic blood pressure (SBP) in SHR, but had no effects in WKY. Intraperitoneal injection of

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... in (50 mg/kg) into SHR also caused a significant reduction in SBP. The depressor effect was significantly inhibited by a nitric oxide synthase inhibitor, N G -nitro-L -arginine methyl ester. Moreover, hesperetin (10 Ϫ 5 M ) enhanced endothelium-dependent relaxation induced by acetylcholine, but had no effect on endothelium-independent relaxation induced by sodium nitroprusside in isolated aortas from SHR. These data suggest that the hypotensive effect of hesperetin in SHR is associated with nitric oxide-mediated vasodilation. Therefore, this effect may be involved in the mechanisms by which G-hesperidin lowers blood pressure in hypertension.