Resveratrol Decrease Fructose-Induced Oxidative Stress Mediated by NADPH Oxidase via an AMPK-Dependent Mechanism.

British journal of pharmacology

PubMedID: 24547812

Cheng PW, Ho WY, Su YT, Lu PJ, Chen BZ, Cheng WH, Lu WH, Sun GC, Yeh TC, Hsiao M, Tseng CJ. Resveratrol Decrease Fructose-Induced Oxidative Stress Mediated by NADPH Oxidase via an AMPK-Dependent Mechanism. Br J Pharmacol. 2014;.
BACKGROUND AND PURPOSE
Oxidative stress is an important pathogenic factor in the development of hypertension. Resveratrol, an important antioxidant in red wine, improves NO bioavailability to prevent cardiovascular disease. The aim of this study was to examine whether resveratrol decreased ROS generation, thereby reducing blood pressure in rats with fructose-induced hypertension.

EXPERIMENTAL APPROACH
The fructose (fed with 10% fructose) or resveratrol (10 mg/kg/day) treatment for 1 week, then the systolic blood pressure (SBP) of the rats was measured by tail-cuff method. Endogenous in vivo O2 (-) production in the NTS was determined with dihydroethidium (DHE). Real-time PCR and immunoblotting analyses were used to quantify RNA and protein expression levels.

KEY RESULTS
ROS levels in the NTS was higher, by contrast, the NO level was significantly decreased in fructose-fed rats. The RNA and protein levels of NADPH oxidase subunits (p67, p22-phox) were elevated and that SOD2 was reduced in fructose-fed rats. In addition, AMPK T172 phosphorylation levels in the NTS were lower in fructose-fed rats, while treatment with an AMPK activator (resveratrol) had the opposite effect in the fructose-fed rats. Interestingly, BP was significantly reduced in fructose-fed rats both by the administration of resveratrol beginning at week 0 and by treatment with resveratrol beginning at week 2; the NO level in the NTS was significantly increased.

CONCLUSIONS AND IMPLICATIONS
Collectively, resveratrol decreased BP through the phosphorylation of AMPK, AKT, and nNOS in fructose-fed rats. These novel findings suggest that the resveratrol may be a potential pharmacological candidate for the treatment of hypertension.