Renal protective effects of N-acetyl-Ser-Asp-Lys-Pro in deoxycorticosterone acetate-salt hypertensive mice.

Abstract

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
• Journal: Journal of hypertension (J Hypertens) Vol. 29 Issue 2 Pg. 330-8 (Feb 2011) ISSN: 1473-5598 [Electronic] England
• PMID: 21052020 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Membrane Proteins
• Oligopeptides
• Sodium Chloride, Dietary
• nephrin
• Desoxycorticosterone
• Collagen
• goralatide

Topics

• 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)