Capsaicin pretreatment attenuates salt-sensitive hypertension by alleviating AMPK/Akt/Nrf2 pathway in hypothalamic paraventricular nucleus

Abstract

Abstract Long term hypertension seriously affects target organ damage such as the brain, heart, and kidneys, and has become an increasingly serious public health problem worldwide. Capsaicin has been proven to improve blood pressure. However, whether capsaicin can reduce salt induced hypertension and the mechanism has yet to be elucidated. This study aimed to identify the AMPK/Akt/iNOS pathway in hypothalamic paraventricular nucleus (PVN) mediates capsaicin in improving the process of high salt induced hypertension. Dahl salt-sensitive (Dahl S) rats were uesed as the animal model for the present study. All rats were randomly divided into four groups based on their dietary regimen (0.3% salt diet and 8% salt diet) and treatment methods. Chronic administration capsaicin to the PVN during the process of blood pressure rise in rats. The entire process lasted for 6 weeks. Our results demonstrated that PVN pretreatment with capsaicin can slow down the blood pressure elevation and heart rate (HR) of Dahl S hypertensive rats. Interestingly, The cardiac hypertrophy was significantly improved. Furthermore, PVN pretreatment with capsaicin induced decrease in mRNA expression of NOX2, Inducible nitric oxide synthase (iNOS), NOX4 and proinfammatory cytokines and increase in positive cell level of Nrf2, p-IKKβ, iNOS and HO-1 in the PVN of Dahl S hypertensive rats. Additionally, the protein expressions of phosphorylated adenosine Monophosphate-activated protein kinase (p-AMPK), the phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase-B (p-AKT) were attenuated after PVN pretreatment with capsaicin. Capsaicin pretreatment attenuates salt-sensitive hypertension by alleviating AMPK/Akt/iNOS pathway in the PVN.