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. 2018 Nov 12;10(11):1741.
doi: 10.3390/nu10111741.

VSports手机版 - Effects of Resveratrol on the Renin-Angiotensin System in the Aging Kidney

In-Ae Jang  1 , Eun Nim Kim  2 , Ji Hee Lim  3 , Min Young Kim  4 , Tae Hyun Ban  5   6 , Hye Eun Yoon  7   8 , Cheol Whee Park  9   10 , Yoon Sik Chang  11   12 , Bum Soon Choi  13   14
Affiliations

Effects of Resveratrol on the Renin-Angiotensin System in the Aging Kidney

In-Ae Jang et al. Nutrients. .

Abstract (V体育平台登录)

The renin-angiotensin system (RAS), especially the angiotensin II (Ang II)/angiotensin II type 1 receptor (AT1R) axis, plays an important role in the aging process of the kidney, through increased tissue reactive oxygen species production and progressively increased oxidative stress. In contrast, the angiotensin 1-7 (Ang 1-7)/Mas receptor (MasR) axis, which counteracts the effects of Ang II, is protective for end-organ damage. To evaluate the ability of resveratrol (RSV) to modulate the RAS in aging kidneys, eighteen-month-old male C57BL/6 mice were divided into two groups that received either normal mouse chow or chow containing resveratrol, for six months. Renal expressions of RAS components, as well as pro- and antioxidant enzymes, were measured and mouse kidneys were isolated for histopathology. Resveratrol-treated mice demonstrated better renal function and reduced albuminuria, with improved renal histologic findings VSports手机版. Resveratrol suppressed the Ang II/AT1R axis and enhanced the AT2R/Ang 1-7/MasR axis. Additionally, the expression of nicotinamide adenine dinucleotide phosphate oxidase 4, 8-hydroxy-2'-deoxyguanosine, 3-nitrotyrosine, collagen IV, and fibronectin was decreased, while the expression of endothelial nitric oxide synthase and superoxide dismutase 2 was increased by resveratrol treatment. These findings demonstrate that resveratrol exerts protective effects on aging kidneys by reducing oxidative stress, inflammation, and fibrosis, through Ang II suppression and MasR activation. .

Keywords: aging; angiotensin converting enzyme 2; kidney; renin-angiotensin system; resveratrol. V体育安卓版.

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Conflict of interest statement

The authors declare no conflict of interest.

"V体育官网" Figures

Figure 1
Figure 1
Effects of resveratrol on renal function of eighteen-month-old male C57BL/6 mice. Compared to the control group, resveratrol group showed (a) lower serum creatinine, (b) increased creatinine clearance, and (c) reduced 24 h albuminuria (* p < 0.05, *** p < 0.001).
Figure 2
Figure 2
Effects of resveratrol on aging-related histological renal injury. (a) Representative photomicrographs of the periodic acid–Schiff-(PAS)-stained kidney showed less expansion of the mesangial area in the RSV group (original magnification 400×). (b) Representative sections of the Masson’s trichrome-stained kidney showed significantly less tubulointerstitial fibrosis in the RSV group (original magnification 200×). (c) Quantitative assessments of the areas of extracellular matrix in the glomerulus. (d) Quantitative assessment of the areas of tubulointerstitial fibrosis in the control and RSV groups (** p < 0.01, *** p < 0.001).
Figure 3
Figure 3
Effects of resveratrol on the expression of prorenin receptors. (a) Representative western blot analysis of prorenin receptors expression. (b) Prorenin receptors levels were decreased in the RSV group. Quantitative analysis of the results is shown (**** p < 0.0001).
Figure 4
Figure 4
Effects of resveratrol on the angiotensin converting enzyme (ACE) and ACEII protein expressions. (a) Representative western blots of ACE and ACEII protein levels. (b) The protein levels of ACE were lower in the RSV group than in the control (Cont.) group. (c) The protein levels of ACEII were higher in the RSV group than in the control group. Quantitative analysis of the results is shown (* p < 0.05).
Figure 5
Figure 5
Effects of resveratrol on the Ang II. (a) Representative images of immunohistochemical staining with Ang II in aging kidney glomerulus (original magnification 200×). (b) The expression of Ang II in kidney was significantly decreased in the RSV group. (c) Ang II-positive area in kidney were observed to be significantly smaller in the RSV group; (d) The expression of Ang II in serum was also significantly decreased in the RSV group (* p < 0.05, *** p < 0.001, **** p < 0.0001).
Figure 6
Figure 6
Effects of resveratrol on the AT1R and AT2R. (a) Representative western blots of AT1R and AT2R. (b) The expression of AT1R was significantly decreased in the RSV group. (c) The expression of AT2R was significantly increased in the RSV group. (d) Representative images of immunohistochemistry for AT1R and AT2R, in the aging kidney glomerulus (original magnification × 200). (e) The expression of AT1R-positive area in the kidney was markedly decreased in the RSV group. (f) The expression of AT2R-positive area in the kidney was markedly increased in the RSV group (* p < 0.05, ** p < 0.01, **** p < 0.0001).
Figure 7
Figure 7
ELISA for serum and kidney levels of Ang 1-7. (a) Renal levels of Ang 1-7 significantly increased in the RSV group, compared to Cont. groups. (b) Serum levels of Ang 1-7 significantly increased in the RSV group, compared to Cont. groups. Quantitative analysis of the results is shown (* p < 0.05).
Figure 8
Figure 8
Effects of resveratrol on MasR. (a) Representative images of immunohistochemical staining of MasR in the aging kidney glomerulus (original magnification 200×). (b) Representative western blots of MasR. (c) MasR-positive area in the kidney was significantly increased in the RSV group. (d) The expression of MasR was significantly increased in the RSV group (* p < 0.05, **** p < 0.0001).
Figure 9
Figure 9
Effects of resveratrol on NOX2 and NOX4. (a) Representative western blots of NOX2 and NOX4 levels. (b) The expression of NOX2 showed a tendency of decrease in the RSV group, compared with the Cont. group, but it was not statistically significant. (c) The expression of Nox4 was significantly decreased in the RSV group. Quantitative analysis of the results is shown (** p < 0.01).
Figure 10
Figure 10
Effects of resveratrol on renal oxidative stress. (a) Representative images of immunohistochemistry for 8-OHdG in aging kidney glomerulus (original magnification 200×). (b) The positive area expression of 8-OHdG in the renal tissue was decreased in the RSV group, compared to that in the Cont. group. (c) Representative images of immunohistochemistry for 3-Nitrotyrosine in the aging kidney glomerulus (original magnification 200×). (d) The positive area expression of 3-Nitrotyrosine in the renal tissue was also decreased in the RSV group (**** p < 0.0001).
Figure 11
Figure 11
Effects of resveratrol on phospho-Ser1177eNOS/eNOS. (a) Representative western blots of phospho-Ser1177eNOS/eNOS levels. (b) The expression of phospho-Ser1177eNOS/eNOS was significantly increased in the RSV group. Quantitative analysis of the results is shown (* p < 0.05).
Figure 12
Figure 12
Effects of resveratrol on SOD1 and SOD2. (a) Representative western blots of SOD1 and SOD2 levels. (b) The expression of SOD1 showed a tendency of increase in the RSV group, compared with the Cont. group, but it was not statistically significant. (c) The expression of SOD2 was significantly increased in the RSV group. Quantitative analysis of the results is shown (* p < 0.05).
Figure 13
Figure 13
Effects of resveratrol on the TGF-β, collagen IV and fibronectin. (a) Representative western blots of TGF-β, collagen IV and fibronectin levels. (b) The expression of TGF-β showed a tendency of decrease in the RSV group, compared with the Cont. group, but it was not statistically significant. (c,d) The expression of collagen IV and fibronectin was significantly decreased in the RSV group. Quantitative analysis of the results is shown (* p < 0.05).
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