title: Resveratrol restored Nrf2 function, reduced renal inflammation, and mitigated hypertension in spontaneously hypertensive rats.
abstract: Compelling evidence supports the role of oxidative stress and renal interstitial inflammation in the pathogenesis of hypertension. Resveratrol is a polyphenolic stilbene, which can lower oxidative stress by activating the transcription factor nuclear factor-E2-related factor-2 (Nrf2), the master regulator of numerous genes encoding antioxidant and phase II-detoxifying enzymes and molecules. Given the role of oxidative stress and inflammation in the pathogenesis of hypertension, we conducted this study to test the hypothesis that long-term administration of resveratrol will attenuate renal inflammation and oxidative stress and, hence, progression of hypertension in the young spontaneously hypertensive rats (SHR). SHR and control [Wistar-Kyoto (WKY)] rats were treated for 9 wk with resveratrol or vehicle in their drinking water. Vehicle-treated SHR exhibited renal inflammatory injury and oxidative stress, as evidenced by glomerulosclerosis, tubulointerstitial injury, infiltration of inflammatory cells, and increased levels of renal 8-isoprostane and protein carbonylation. This was associated with reduced antioxidant capacity and downregulations of Nrf2 and phase II antioxidant enzyme glutathione-S-transferase (GST). Resveratrol treatment mitigated renal inflammation and injury, reduced oxidative stress, normalized antioxidant capacity, restored Nrf2 and GST activity, and attenuated the progression of hypertension in SHR. However, resveratrol had no effect on these parameters in WKY rats. In conclusion, development and progression of hypertension in the SHR are associated with inflammation, oxidative stress, and impaired Nrf2-GST activity in the kidney. Long-term administration of resveratrol restores Nrf2 expression, ameliorates inflammation, and attenuates development of hypertension in SHR. Clinical studies are needed to explore efficacy of resveratrol in human hypertension.
authors.affiliation: Heart and Kidney Institute, College of Pharmacy, University of Houston, Houston Texas;
authors.forename: Apurva A
authors.initials: AA
authors.lastname: Javkhedkar
authors.affiliation: Hospital Universitario, Universidad del Zulia and Instituto Venezolano de Investigaciones Científicas-Zulia, Maracaibo, Venezuela; and.
authors.forename: Yasmir
authors.initials: Y
authors.lastname: Quiroz
authors.affiliation: Hospital Universitario, Universidad del Zulia and Instituto Venezolano de Investigaciones Científicas-Zulia, Maracaibo, Venezuela; and.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Rodriguez-Iturbe
authors.affiliation: Division of Nephrology and Hypertension, University of California, Irvine, California.
authors.forename: Nosratola D
authors.initials: ND
authors.lastname: Vaziri
authors.affiliation: Heart and Kidney Institute, College of Pharmacy, University of Houston, Houston Texas;
authors.forename: Mustafa F
authors.initials: MF
authors.lastname: Lokhandwala
authors.affiliation: Heart and Kidney Institute, College of Pharmacy, University of Houston, Houston Texas; abanday@uh.edu.
authors.forename: Anees A
authors.initials: AA
authors.lastname: Banday
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D013267:Stilbenes; D000077185:Resveratrol
keywords: hypertension; oxidative stress; proximal tubules