Angiotensin-(1-7) reduces proteinuria and diminishes structural damage in renal tissue of stroke-prone spontaneously hypertensive rats.
Angiotensin (ANG)-(1-7) constitutes an important functional end-product of the renin-angiotensin-aldosterone system that acts to balance the physiological actions of ANG II. In the kidney, ANG-(1-7) exerts beneficial effects by inhibiting growth-promoting pathways and reducing proteinuria. We examined whether a 2-wk treatment with a daily dose of ANG-(1-7) (0.6 mg·kg(-1)·day(-1)) exerts renoprotective effects in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). Body weight, glycemia, triglyceridemia, cholesterolemia, as well as plasma levels of Na+ and K+ were determined both at the beginning and at the end of the treatment. Also, the weekly evolution of arterial blood pressure, proteinuria, and creatinine clearance was evaluated. Renal fibrosis was determined by Masson's trichrome staining. Interleukin (IL)-6, tumor necrosis factor (TNF)-α, and nuclear factor-κB (NF-κB) levels were determined by immunohistochemistry and confirmed by Western blotting analysis. The levels of glomerular nephrin were assessed by immunofluorescence. Chronic administration of ANG-(1-7) normalized arterial pressure, reduced glycemia and triglyceridemia, improved proteinuria, and ameliorated structural alterations in the kidney of SHRSP as shown by a restoration of glomerular nephrin levels as detected by immunofluorescence. These results were accompanied with a decrease in both the immunostaining and abundance of IL-6, TNF-α, and NF-κB. In this context, the current study provides strong evidence for a protective role of ANG-(1-7) in the kidney.
IQUIFIB, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 (1113 Buenos Aires, Argentina.
Jorge F
JF
Giani
Marina C
MC
Muñoz
Romina A
RA
Pons
Gabriel
G
Cao
Jorge E
JE
Toblli
Daniel
D
Turyn
Fernando P
FP
Dominici
D000803:Angiotensin I / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015850:Interleukin-6 / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010446:Peptide Fragments / Q000627:therapeutic use*; D011507:Proteinuria / Q000188:drug therapy*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012965:Sodium Chloride / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015850:Interleukin-6; D008565:Membrane Proteins; D016328:NF-kappa B; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C113267:nephrin; D012965:Sodium Chloride; D000803:Angiotensin I; C118790:angiotensin I (1-7)