Molecular and Cellular Effect of Angiotensin 1–7 on Hypertensive Kidney Disease
| Autor: | Yuanjian Chen, Yao Sun, Syamal K. Bhattacharya, Chang Liu, Tieqiang Zhao, Wenyuan Zhao, Weixin Meng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
medicine.medical_specialty Hypertension Renal Sympathetic Nervous System Original Contributions Blotting Western Vascular Endothelial Growth Factor D Blood Pressure 030204 cardiovascular system & hematology medicine.disease_cause Kidney Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Hypertensive Nephropathy Renin–angiotensin system Internal Medicine Renal fibrosis medicine Animals Humans 030212 general & internal medicine Antihypertensive Agents Platelet-Derived Growth Factor Lymphokines Aldosterone Nephritis business.industry Tissue Inhibitor of Metalloproteinases medicine.disease Fibrosis Peptide Fragments Rats Hypertensive kidney disease Disease Models Animal Oxidative Stress Blood pressure Endocrinology medicine.anatomical_structure chemistry Gene Expression Regulation RNA Angiotensin I business Oxidative stress |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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