Glut5‐KD reduces blood pressure via increases phosphorylation of nNOS and decreases NADPH oxidase by AMPK activation in the NTS of fructose‐induced hypertensive rats

Abstract

Glucose transporter5 (GLUT5) is a fructose transporter in enterocytes. Many studies indicated that the mechanisms by which excessive fructose increases blood pressure. GLUT5 immunoreactivity is located in the epithelial cells of the choroid plexus and the ependymal cells, suggesting the possibility of the direct transportation of intravascular fructose into the nucleus tractus solitarii (NTS). The aim of this study was to investigate whether knock‐down GLUT5 in the NTS can improve hypertension in fructose‐fed rats with 10% fructose water. Our in vivo study showed that GLUT1/5 mRNA levels increased in the NTS of fructose‐fed rats at the early stage of 7 days. Our in vitro immunoblotting study found that fructose‐induced GLUT5 up‐regulated lead to AKT‐nNOS signaling pathway significantly decreased in PC12 neuronal cells after fructose treatment. In addition, we injected lentivirus‐delivered GLUT5 shRNA into the NTS of fructose‐induced hypertensive rats for 6 weeks. Two weeks after injection of lentivirus‐delivered GLUT5 shRNA, we fed with 10% fructose water for 4 weeks. Glut5‐knockdown (KD) down‐regulates blood pressure through improved sympathetic hyperactivity and central insulin signaling in the fructose‐induced hypertensive rats. Our data showed that Glut5‐KD restores AMPK‐dependent mechanism, decreases fructose‐induced oxidative stress, which attenuated NADPH oxidase in the NTS of fructose‐induced hypertensive rats. This study suggests that fructose through GLUT5‐RAGE overexpression induces ROS generation in the NTS, which lead to impairment of AKT‐nNOS‐NO signaling pathway and cause hypertension.Support or Funding InformationMOST104‐2320‐B‐075B‐003‐MY3, 107‐2320‐B‐075B‐002‐MY2This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.