Our results indicate that resveratrol decreased blood pressure during fructose-induced hypertension by activating AMPK, which in turn abolished the generation of ROS, induced SOD2 via lowering the activity of Rac1-induced NADPH oxidase, enhancing the activity of the ERK1/2-RSK-nNOS signaling pathway in the brain. Here, PRKAA1 is linked to hypertensive disorder.