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Angiotensin(1-7) attenuates the progression of streptozotocin-induced diabetic renal injury better than angiotensin receptor blockade.

Zhang K, Meng X, Li D, Yang J, Kong J, Hao P, Guo T, Zhang M, Zhang Y, Zhang C - Kidney Int. (2014)

Bottom Line: A779 blocked the effects of Ang(1-7) both in vivo and in vitro.The effects of large-dose Ang(1-7) alone and in combination with valsartan were superior to valsartan alone, but the combination had no significant synergistic effect compared with Ang(1-7) alone.Large-dose treatment was superior to valsartan in reducing oxidative stress and inhibiting TGFβ1/Smad3- and VEGF-mediated pathways.

View Article: PubMed Central - PubMed

Affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China.

ABSTRACT
To explore the potential therapeutic effects of angiotensin(1-7) (Ang(1-7)), an endogenous ligand of the Mas receptor, on streptozotocin-induced diabetic nephropathy, male Wistar rats were randomly divided into two groups: a control group and a diabetic model group. After 12 weeks, the diabetic rats were divided into subgroups for 4-week treatments consisting of no-treatment group, small-, moderate-, and large-dose Ang(1-7) groups, a valsartan group, a large-dose Ang(1-7) plus valsartan group, and an A779 (antagonist of the Mas receptor) group, each with 15 rats. Ang(1-7) improved renal function, attenuated glomeruli sclerosis, oxidative stress, and cell proliferation, decreased the expression of collagen IV, TGF-β1, VEGF, NOX4, p47phox, PKCα, and PKCβ1, and the phosphorylation of Smad3. In the rat mesangial HBZY-1 cell line, Ang(1-7) decreased high-glucose-induced oxidative stress, the proliferation and expression of NOX4, p47phox, and TGF-β1, the phosphorylation of Smad3, collagen IV, and VEGF, and the membrane translocation of PKCα and PKCβ1. A779 blocked the effects of Ang(1-7) both in vivo and in vitro. The effects of large-dose Ang(1-7) alone and in combination with valsartan were superior to valsartan alone, but the combination had no significant synergistic effect compared with Ang(1-7) alone. Thus, Ang(1-7) ameliorated streptozotocin-induced diabetic renal injury. Large-dose treatment was superior to valsartan in reducing oxidative stress and inhibiting TGFβ1/Smad3- and VEGF-mediated pathways.

No MeSH data available.


Related in: MedlinePlus

Effect of Ang(1–7) and valsartan treatment on oxidative stress and cell proliferation in HBZY-1 cells. (a) Representative dihydroethidium (DHE), dichlorofluorescein (DCF), and 5-ethynyl-2′-deoxyuridine (EdU) staining in HBZY-1 cells. (b) Quantitative analysis of DHE staining. (c) Quantitative analysis of DCF staining. (d) Quantitative analysis of EdU staining. *P<0.05 vs. the control group; #P<0.05 vs. the high-glucose group; §P<0.05 vs. the valsartan group. HG: high glucose (25 mmol/l); S-Ang(1–7): small-dose Ang(1–7) (50 nmol/l); M-Ang(1–7): moderate-dose Ang(1–7) (100 nmol/l); L-Ang(1–7): large-dose Ang(1–7) (200 nmol/l); valsartan: 10−6 mol/l valsartan; L+V, large-dose Ang(1–7)+valsartan; L+A779, large-dose Ang(1–7)+A779 (200 nmol/l).
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fig4: Effect of Ang(1–7) and valsartan treatment on oxidative stress and cell proliferation in HBZY-1 cells. (a) Representative dihydroethidium (DHE), dichlorofluorescein (DCF), and 5-ethynyl-2′-deoxyuridine (EdU) staining in HBZY-1 cells. (b) Quantitative analysis of DHE staining. (c) Quantitative analysis of DCF staining. (d) Quantitative analysis of EdU staining. *P<0.05 vs. the control group; #P<0.05 vs. the high-glucose group; §P<0.05 vs. the valsartan group. HG: high glucose (25 mmol/l); S-Ang(1–7): small-dose Ang(1–7) (50 nmol/l); M-Ang(1–7): moderate-dose Ang(1–7) (100 nmol/l); L-Ang(1–7): large-dose Ang(1–7) (200 nmol/l); valsartan: 10−6 mol/l valsartan; L+V, large-dose Ang(1–7)+valsartan; L+A779, large-dose Ang(1–7)+A779 (200 nmol/l).

Mentions: The level of reactive oxygen species (ROS) in glomerular mesangial HBZY-1 cells, as determined by dihydroethidium and dichlorofluorescein staining, was significantly increased after high glucose stimulation (P<0.05, Figure 4a–c). The content of ROS was dose-dependently attenuated by Ang(1–7) treatment, but this effect was virtually offset by combined A779 treatment (P>0.05, Figure 4a–c). Similar to the in vivo effects, large-dose Ang(1–7) treatment alone or in combination with valsartan reduced ROS content to a greater extent than valsartan treatment alone (P<0.05, Figure 4a–c).


Angiotensin(1-7) attenuates the progression of streptozotocin-induced diabetic renal injury better than angiotensin receptor blockade.

Zhang K, Meng X, Li D, Yang J, Kong J, Hao P, Guo T, Zhang M, Zhang Y, Zhang C - Kidney Int. (2014)

Effect of Ang(1–7) and valsartan treatment on oxidative stress and cell proliferation in HBZY-1 cells. (a) Representative dihydroethidium (DHE), dichlorofluorescein (DCF), and 5-ethynyl-2′-deoxyuridine (EdU) staining in HBZY-1 cells. (b) Quantitative analysis of DHE staining. (c) Quantitative analysis of DCF staining. (d) Quantitative analysis of EdU staining. *P<0.05 vs. the control group; #P<0.05 vs. the high-glucose group; §P<0.05 vs. the valsartan group. HG: high glucose (25 mmol/l); S-Ang(1–7): small-dose Ang(1–7) (50 nmol/l); M-Ang(1–7): moderate-dose Ang(1–7) (100 nmol/l); L-Ang(1–7): large-dose Ang(1–7) (200 nmol/l); valsartan: 10−6 mol/l valsartan; L+V, large-dose Ang(1–7)+valsartan; L+A779, large-dose Ang(1–7)+A779 (200 nmol/l).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4317508&req=5

fig4: Effect of Ang(1–7) and valsartan treatment on oxidative stress and cell proliferation in HBZY-1 cells. (a) Representative dihydroethidium (DHE), dichlorofluorescein (DCF), and 5-ethynyl-2′-deoxyuridine (EdU) staining in HBZY-1 cells. (b) Quantitative analysis of DHE staining. (c) Quantitative analysis of DCF staining. (d) Quantitative analysis of EdU staining. *P<0.05 vs. the control group; #P<0.05 vs. the high-glucose group; §P<0.05 vs. the valsartan group. HG: high glucose (25 mmol/l); S-Ang(1–7): small-dose Ang(1–7) (50 nmol/l); M-Ang(1–7): moderate-dose Ang(1–7) (100 nmol/l); L-Ang(1–7): large-dose Ang(1–7) (200 nmol/l); valsartan: 10−6 mol/l valsartan; L+V, large-dose Ang(1–7)+valsartan; L+A779, large-dose Ang(1–7)+A779 (200 nmol/l).
Mentions: The level of reactive oxygen species (ROS) in glomerular mesangial HBZY-1 cells, as determined by dihydroethidium and dichlorofluorescein staining, was significantly increased after high glucose stimulation (P<0.05, Figure 4a–c). The content of ROS was dose-dependently attenuated by Ang(1–7) treatment, but this effect was virtually offset by combined A779 treatment (P>0.05, Figure 4a–c). Similar to the in vivo effects, large-dose Ang(1–7) treatment alone or in combination with valsartan reduced ROS content to a greater extent than valsartan treatment alone (P<0.05, Figure 4a–c).

Bottom Line: A779 blocked the effects of Ang(1-7) both in vivo and in vitro.The effects of large-dose Ang(1-7) alone and in combination with valsartan were superior to valsartan alone, but the combination had no significant synergistic effect compared with Ang(1-7) alone.Large-dose treatment was superior to valsartan in reducing oxidative stress and inhibiting TGFβ1/Smad3- and VEGF-mediated pathways.

View Article: PubMed Central - PubMed

Affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China.

ABSTRACT
To explore the potential therapeutic effects of angiotensin(1-7) (Ang(1-7)), an endogenous ligand of the Mas receptor, on streptozotocin-induced diabetic nephropathy, male Wistar rats were randomly divided into two groups: a control group and a diabetic model group. After 12 weeks, the diabetic rats were divided into subgroups for 4-week treatments consisting of no-treatment group, small-, moderate-, and large-dose Ang(1-7) groups, a valsartan group, a large-dose Ang(1-7) plus valsartan group, and an A779 (antagonist of the Mas receptor) group, each with 15 rats. Ang(1-7) improved renal function, attenuated glomeruli sclerosis, oxidative stress, and cell proliferation, decreased the expression of collagen IV, TGF-β1, VEGF, NOX4, p47phox, PKCα, and PKCβ1, and the phosphorylation of Smad3. In the rat mesangial HBZY-1 cell line, Ang(1-7) decreased high-glucose-induced oxidative stress, the proliferation and expression of NOX4, p47phox, and TGF-β1, the phosphorylation of Smad3, collagen IV, and VEGF, and the membrane translocation of PKCα and PKCβ1. A779 blocked the effects of Ang(1-7) both in vivo and in vitro. The effects of large-dose Ang(1-7) alone and in combination with valsartan were superior to valsartan alone, but the combination had no significant synergistic effect compared with Ang(1-7) alone. Thus, Ang(1-7) ameliorated streptozotocin-induced diabetic renal injury. Large-dose treatment was superior to valsartan in reducing oxidative stress and inhibiting TGFβ1/Smad3- and VEGF-mediated pathways.

No MeSH data available.


Related in: MedlinePlus