Document Detail


Renal protective effects of N-acetyl-Ser-Asp-Lys-Pro in deoxycorticosterone acetate-salt hypertensive mice.
MedLine Citation:
PMID:  21052020     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Nour-Eddine Rhaleb; Saraswati Pokharel; Umesh Sharma; Oscar A Carretero
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of hypertension     Volume:  29     ISSN:  1473-5598     ISO Abbreviation:  J. Hypertens.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2010-12-30     Completed Date:  2011-05-04     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  330-8     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Michigan 48202, USA. nrhaleb1@hfhs.org
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MeSH Terms
Descriptor/Qualifier:
Albuminuria / 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:
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:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Membrane Proteins; 0/Oligopeptides; 0/Sodium Chloride, Dietary; 0/nephrin; 64-85-7/Desoxycorticosterone; 9007-34-5/Collagen; H041538E9P/goralatide
Comments/Corrections

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