Yuanjian Chen 1 , Wenyuan Zhao 1 , Chang Liu 1 , Weixin Meng 1 , Tieqiang Zhao 1 , Syamal K Bhattacharya 1 , Yao Sun 1 Show Affiliations »
Abstract
BACKGROUND: Studies implicate that angiotensin 1-7 (Ang1-7) imparts protective effects in the kidney. However, its relevance in hypertensive kidney disease is not fully understood. The purpose of this study was to explore the role of Ang1-7 on renal damage/remodeling during hypertension and its potential underlying molecular-cellular mechanisms. METHODS: Hypertension was induced in adult Sprague-Dawley rats by infusion of aldosterone (ALDO; 0.75 μg/hour) for 4 weeks with or without co-treatment of Ang1-7 (1 mg/kg/day). Untreated rats served as controls. Systolic blood pressure was monitored by tail-cuff technique. Renal fibrosis was evaluated by picrosirius red staining and renal collagen volume fraction was quantitated using imaging analyzing system. The expression of profibrotic factors [transforming growth factor-β1 (TGF-β1), platelet-derived growth factor-D (PDGF-D), fibroblast growth factor-1 (FGF-1), vascular endothelial growth factor-D (VEGF-D), and tissue inhibitors of metalloproteinases (TIMPs)] and free radical producing enzymes (inducible nitric oxide synthase and nicotinamide adenine dinucleotide phosphate [NADPH] oxidase) in the kidney were examined by reverse transcription-polymerase chain reaction and western blot. Renal oxidative stress was assessed by malondialdehyde (MDA) measurement. RESULTS: Chronic ALDO infusion caused hypertension and hypertensive renal disease represented as glomerular damage/sclerosis. Ang1-7 co-treatment did not affect blood pressure in ALDO-treated rats, but significantly attenuated the glomerular damage/fibrosis. ALDO treatment significantly elevated renal expression of profibrogenic factors, including TGF-β1, TIMP-1/TIMP-2, FGF-1, PDGF-D, and VEGF-D, whereas Ang1-7 co-treatment significantly reduced renal TGF-β1, TIMP-1/TIMP-2, and FGF-1, but not PDGF-D and VEGF-D. Furthermore, ALDO infusion elevated NADPH oxidase (gp91phox) and MDA in the kidney, which was attenuated by Ang1-7 co-treatment. CONCLUSIONS: Ang1-7 plays a protective role in the hypertensive kidney disease independent of blood pressure. The beneficial effects of Ang1-7 are likely mediated via suppressing TGF-β/FGF-1 pathways and oxidative stress. © American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
BACKGROUND: Studies implicate that angiotensin 1-7 (Ang1-7 ) imparts protective effects in the kidney. However, its relevance in hypertensive kidney disease is not fully understood. The purpose of this study was to explore the role of Ang1-7 on renal damage /remodeling during hypertension and its potential underlying molecular-cellular mechanisms. METHODS: Hypertension was induced in adult Sprague-Dawley rats by infusion of aldosterone (ALDO ; 0.75 μg/hour) for 4 weeks with or without co-treatment of Ang1-7 (1 mg/kg/day). Untreated rats served as controls. Systolic blood pressure was monitored by tail-cuff technique. Renal fibrosis was evaluated by picrosirius red staining and renal collagen volume fraction was quantitated using imaging analyzing system. The expression of profibrotic factors [transforming growth factor-β1 (TGF-β1), platelet-derived growth factor-D (PDGF-D ), fibroblast growth factor-1 (FGF-1 ), vascular endothelial growth factor-D (VEGF-D ), and tissue inhibitors of metalloproteinases (TIMPs)] and free radical producing enzymes (inducible nitric oxide synthase and nicotinamide adenine dinucleotide phosphate [NADPH] oxidase) in the kidney were examined by reverse transcription-polymerase chain reaction and western blot. Renal oxidative stress was assessed by malondialdehyde (MDA ) measurement. RESULTS: Chronic ALDO infusion caused hypertension and hypertensive renal disease represented as glomerular damage/sclerosis . Ang1-7 co-treatment did not affect blood pressure in ALDO -treated rats , but significantly attenuated the glomerular damage /fibrosis . ALDO treatment significantly elevated renal expression of profibrogenic factors, including TGF-β1, TIMP-1 /TIMP-2 , FGF-1 , PDGF-D , and VEGF-D , whereas Ang1-7 co-treatment significantly reduced renal TGF-β1, TIMP-1 /TIMP-2 , and FGF-1 , but not PDGF-D and VEGF-D . Furthermore, ALDO infusion elevated NADPH oxidase (gp91phox ) and MDA in the kidney, which was attenuated by Ang1-7 co-treatment. CONCLUSIONS: Ang1-7 plays a protective role in the hypertensive kidney disease independent of blood pressure. The beneficial effects of Ang1-7 are likely mediated via suppressing TGF-β/FGF-1 pathways and oxidative stress. © American Journal of Hypertension , Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Entities: Chemical
Disease
Gene
Species
Keywords:
angiotensin 1–7; blood pressure; fibrotic mediators; hypertension; hypertensive kidney disease; oxidative stress
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Year: 2019
PMID： 30715105 PMCID： PMC6475878 DOI： 10.1093/ajh/hpz009
Source DB: PubMed Journal: Am J Hypertens ISSN： 0895-7061 Impact factor: 2.689