The purpose of this study was to determine whether improve nitric oxide (NO) release in the brain, either through the activation of AMP-activated protein kinase (AMPK) or reduced Ras-related C3 botulinum toxin substrate 1 (Rac1)-induced reactive oxygen species (ROS) generation, thereby reducing blood pressure (BP) in rats with fructose-induced hypertension.
These results, for the first time, identified that the precise signaling pathway of RAS regulating ROS in PVN is via AT1R/PKCγ/Rac1 in salt-induced hypertension.
Notably, salt loading increases renal Rac1 activity in several models of salt-sensitive hypertension, which, in the presence of aldosterone, synergistically activates MR signaling, causing hypertension and kidney injury.
The emerging concept of 'ligand-independent aberrant mineralocorticoid receptor activation by Rac1' in the pathogenesis of salt-sensitive hypertension and kidney injury has been reviewed.