| Renal protective effects of N-acetyl-Ser-Asp-Lys-Pro in deoxycorticosterone acetate-salt hypertensive mice. | |
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MedLine Citation:
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PMID: 21052020 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Hypertension-induced renal injury is characterized by inflammation, fibrosis and proteinuria. Previous studies have demonstrated that N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP) inhibits renal damage following diabetes mellitus and antiglomerular basement membrane nephritis. However, its effects on low-renin hypertensive nephropathy are not known. Thus, we hypothesized that Ac-SDKP has renal protective effects on deoxycorticosterone acetate (DOCA)-salt hypertensive mice, decreasing inflammatory cell infiltration, matrix deposition and albuminuria. METHOD: We uninephrectomized 16-week-old C57BL/6J mice and treated them with either placebo, DCOA (10 mg/10 g body weight subcutaneous) and 1% sodium chloride with 0.2% potassium chloride in drinking water (DOCA-salt) or DOCA-salt with Ac-SDKP (800 μg/kg per day) for 12 weeks. We measured blood pressure, urine albumin, glomerular matrix, renal collagen content, monocyte/macrophage infiltration and glomerular nephrin expression. RESULTS: Treatment with DOCA-salt significantly increased blood pressure (P < 0.01), which remained unaltered by Ac-SDKP. Ac-SDKP decreased DOCA-salt-induced renal collagen deposition, glomerular matrix expansion and monocyte/macrophage infiltration. Moreover, DOCA-salt-induced increase in albuminuria was normalized by Ac-SDKP (controls, 10.8 ± 1.7; DOCA-salt, 41 ± 5; DOCA-salt + Ac-SDKP, 13 ± 3 μg/10 g body weight per 24 h; P < 0.001, DOCA-salt vs. DOCA-salt + Ac-SDKP). Loss of nephrin reportedly causes excess urinary protein excretion; therefore, we determined whether Ac-SDKP inhibits proteinuria by restoring nephrin expression in the glomerulus of hypertensive mice. DOCA-salt significantly downregulated glomerular nephrin expression (controls, 37 ± 8; DOCA-salt, 10 ± 1.5% of glomerular area; P < 0.01), which was partially reversed by Ac-SDKP (23 ± 4.0% of glomerular area; P = 0.065, DOCA-salt vs. DOCA-salt + Ac-SDKP). CONCLUSION: We concluded that Ac-SDKP prevents hypertension-induced inflammatory cell infiltration, collagen deposition, nephrin downregulation and albuminuria, which could lead to renoprotection in hypertensive mice. |
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Authors:
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Nour-Eddine Rhaleb; Saraswati Pokharel; Umesh Sharma; Oscar A Carretero |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Journal of hypertension Volume: 29 ISSN: 1473-5598 ISO Abbreviation: J. Hypertens. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2010-12-30 Completed Date: 2011-05-04 Revised Date: 2012-02-02 |
Medline Journal Info:
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Nlm Unique ID: 8306882 Medline TA: J Hypertens Country: England |
Other Details:
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Languages: eng Pagination: 330-8 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Michigan 48202, USA. nrhaleb1@hfhs.org |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Albuminuria
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etiology,
prevention & control Angiotensin-Converting Enzyme Inhibitors / pharmacology Animals Blood Pressure / drug effects Collagen / metabolism Desoxycorticosterone / toxicity* Hypertension, Renal / etiology*, pathology, physiopathology, prevention & control* Kidney / drug effects*, pathology, physiopathology Macrophages / drug effects, pathology Male Membrane Proteins / metabolism Mice Mice, Inbred C57BL Oligopeptides / pharmacology* Sodium Chloride, Dietary / toxicity |
| Grant Support | |
ID/Acronym/Agency:
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HL 071806/HL/NHLBI NIH HHS; HL028982/HL/NHLBI NIH HHS; P01 HL028982-30/HL/NHLBI NIH HHS; R01 HL071806-07/HL/NHLBI NIH HHS; R01 HL071806-08/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin-Converting Enzyme Inhibitors; 0/Membrane Proteins; 0/Oligopeptides; 0/Sodium Chloride, Dietary; 0/nephrin; 120081-14-3/goralatide; 64-85-7/Desoxycorticosterone; 9007-34-5/Collagen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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