Glucosyl hesperidin prevents endothelial dysfunction and oxidative stress in spontaneously hypertensive rats

Glucosyl hesperidin (G-hesperidin), a water-soluble hesperidin derivative, has antihypertensive effects. A detailed understanding of the mechanism of the blood pressure-lowering effect, however, remains obscure. The aim of this work was to investigate the underlying mechanisms involved in the hypotensive effect of G-hesperidin in spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKYs).

Fourteen-week-old SHRs and WKYs were fed a control or G-hesperidin (50 mg/kg) diet for 8 wk. Blood pressure was recorded weekly. After 8 wk, the vasodilatory responses of isolated aortas to acetylcholine and sodium nitroprusside were assessed. Expression of mRNAs related to regulation of blood pressure and vascular tone in the aorta also was investigated. Urinary 8-hydroxy-2'-deoxyguanosine, an oxidative stress marker, was measured. Cardiac and vascular hypertrophies were observed.

In SHRs, the ingestion of G-hesperidin inhibited the development of hypertension. G-hesperidin enhanced endothelium-dependent vasodilation in response to acetylcholine, but had no effect on endothelium-independent vasodilation in response to sodium nitroprusside. G-hesperidin decreased mRNA expression of nicotinamide adenine dinucleotide phosphate oxidase subunits in aorta, which are the main source of superoxide anion in the vasculature; endothelial nitric oxide synthase expression was unchanged. Urinary 8-hydroxy-2'-deoxyguanosine was reduced significantly by G-hesperidin treatment. G-hesperidin suppressed cardiac and vascular hypertrophies. In contrast, G-hesperidin had no effects in WKYs.

Continuous ingestion of G-hesperidin reduces oxidative stress by inhibiting nicotinamide adenine dinucleotide phosphate oxidase expression in the vasculature, thereby ameliorating endothelial dysfunction and hypertension in SHRs.