Antioxidant resveratrol restores renal sodium transport regulation in SHR

Previously we have shown that in spontaneously hypertensive rats (SHR) renal angiotensin (Ang) II receptor ( AT 1R) upregulation leads to overstimulation of Na/K‐ ATP ase by Ang II . There are reports that antioxidants can reduce oxidative stress and blood pressure ( BP ) in SHR , however the effect of these compounds on AT 1R function remains to be determined. Therefore, we hypothesized that polyphenol antioxidant resveratrol would mitigate oxidative stress, normalize renal AT 1R signaling, and reduce BP in SHR . SHR and wistar‐kyoto ( WKY ) rats were treated with resveratrol for 8 weeks. Untreated SHR exhibited oxidative stress and enhanced renal proximal tubular Ang II ‐induced G‐protein activation and Na/K‐ ATP ase stimulation. Treatment of SHR with resveratrol mitigated oxidative stress, reduced BP , and normalized renal AT 1R signaling. In SHR , nuclear expression of transcription factor NF ‐ κB was increased while expression of Nrf2 was reduced. SHR also exhibited a significant decrease in renal antioxidant capacity and activities of phase II antioxidant enzymes. Resveratrol treatment of SHR abolished renal NF ‐ κB activation, restored Nrf2‐phase II antioxidant signaling and Ang II ‐mediated Na/K‐ ATP ase regulation. These data show that in SHR , oxidative stress via activation of NF ‐ κB upregulates AT 1R–G‐protein signaling resulting in overstimulation Na/K‐ ATP ase which contributes to hypertension. Resveratrol, via Nrf2, activates phase II antioxidant enzymes, mitigates oxidative stress, normalizes AT 1R–G‐protein signaling and Na/K‐ ATP ase regulation, and decreases BP in SHR.