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. 2015 May 15;308(10):R840-6.
doi: 10.1152/ajpregu.00308.2014. Epub 2015 Mar 11.

Resveratrol restored Nrf2 function, reduced renal inflammation, and mitigated hypertension in spontaneously hypertensive rats (VSports注册入口)

Apurva A Javkhedkar  1 , Yasmir Quiroz  2 , Bernardo Rodriguez-Iturbe  2 , Nosratola D Vaziri  3 , Mustafa F Lokhandwala  1 , Anees A Banday  4
Affiliations

Resveratrol restored Nrf2 function, reduced renal inflammation, and mitigated hypertension in spontaneously hypertensive rats

Apurva A Javkhedkar et al. Am J Physiol Regul Integr Comp Physiol. .

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 VSports手机版. 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. .

Keywords: hypertension; oxidative stress; proximal tubules V体育安卓版. .

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Figures

Fig. 1.
Fig. 1.
Effect of resveratrol (R) on blood pressure in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Blood pressure was measured continuously from 7 to 12 wk of age. Data are expressed as means ± SE from 6–8 rats. *P < 0.05 vs. untreated SHR at respective time point.
Fig. 2.
Fig. 2.
Effect of resveratrol (R) on oxidative stress in renal proximal tubules from SHR and WKY rats. Proximal tubular 8-isoprostane (A), protein carbonylation (B) and total antioxidant activity (C). Data are expressed as means ± SE from 6–8 rats. *P < 0.05 vs. WKY rats and #P < 0.05 vs. SHR.
Fig. 3.
Fig. 3.
Effect of resveratrol (R) on kidney tubulointerstitial inflammation in SHR and WKY rats. Lymphocytes: CD5+ cells (A), macrophages: CD68+ cells (B), and ANG II-positive cells (C) are all increased in the SHR and reduced by resveratrol treatment. Data are expressed as means ± SE. *P < 0.05 vs. WKY rats and #P < 0.05 vs. SHR.
Fig. 4.
Fig. 4.
Representative kidney microphotographs of the histologic (periodic acid-Schiff staining, row 1), (hematoxylin-and-eosin staining, row 2) and immunohistologic findings (immunoperoxidase; rows 3 and 4) in WKY, SHR treated with resveratrol (SHR-R) and SHR. Light histology is normal in WKY rats and show focal areas of tubular dilation and atrophy in the SHR-R, while SHR rats (untreated) show more extensive tubulointerstitial damage and one glomerulus with a focal (<10%) are of sclerosis. ANG II-positive cells (row 3) are not found in the WKY rats, a small number of tubular cells stain positive for ANG II (arrows) in the SHR-R group and are increased in number, in association with positive infiltrating cells in the SHR control. Lymphocytes (row 4) are scarce in the WKY group and are increased in number in the SHR-R group, and higher numbers of lymphocytes are present in the SHR group.
Fig. 5.
Fig. 5.
Effect of resveratrol (R) on nuclear Nrf2 expression in renal proximal tubules form SHR and WKY rats. Nrf2 nuclear fluorescence intensity (A), bars representing nuclear Nrf2 immunoreactivity (B), and three representative nuclear Nrf2 blots and a histone blot. lane 1, WKY; lane 2, SHR; lane 3, WKY-R; lane 4, SHR-R (C). MW, molecular weight; V, vehicle. Data are expressed as means ± SE from 6–8 rats. *P < 0.05 vs. WKY rats, and #P < 0.05 vs. SHR.
Fig. 6.
Fig. 6.
Effect of resveratrol (R) phase II antioxidant enzymes in renal proximal tubules form SHR and WKY rats. A: glutathione-S-transferase (GST) protein mRNA level. B: bars representing protein content; top: a representative immunoblot: lane 1, WKY; lane 2, SHR; lane 3, WKY-R; and lane 4, SHR-R. Enzymatic activity of GST (C) and superoxide dismutase (SOD) in proximal tubules (D). Data are expressed as means ± SE from 6–8 rats. *P < 0.05 vs. WKY rats, and #P < 0.05 vs. SHR.
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