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Molecular and Cellular Effect of Angiotensin 1-7 on Hypertensive Kidney Disease.
- Source :
-
American journal of hypertension [Am J Hypertens] 2019 Apr 22; Vol. 32 (5), pp. 460-467. - Publication Year :
- 2019
-
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.<br />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.<br />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.<br />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.<br /> (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Animals
Antihypertensive Agents pharmacology
Blood Pressure physiology
Blotting, Western
Disease Models, Animal
Fibrosis genetics
Fibrosis metabolism
Fibrosis pathology
Gene Expression Regulation
Hypertension, Renal metabolism
Hypertension, Renal pathology
Kidney drug effects
Kidney pathology
Lymphokines biosynthesis
Lymphokines genetics
Male
Nephritis metabolism
Nephritis pathology
Platelet-Derived Growth Factor biosynthesis
Platelet-Derived Growth Factor genetics
RNA genetics
Rats
Rats, Sprague-Dawley
Tissue Inhibitor of Metalloproteinases biosynthesis
Tissue Inhibitor of Metalloproteinases genetics
Vascular Endothelial Growth Factor D biosynthesis
Vascular Endothelial Growth Factor D genetics
Angiotensin I pharmacology
Hypertension, Renal drug therapy
Kidney metabolism
Nephritis drug therapy
Oxidative Stress
Peptide Fragments pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1941-7225
- Volume :
- 32
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of hypertension
- Publication Type :
- Academic Journal
- Accession number :
- 30715105
- Full Text :
- https://doi.org/10.1093/ajh/hpz009