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Protective effects of angiotensin‐(1–7) administrated with an angiotensin‐receptor blocker in a rat model of chronic kidney disease
Author(s) -
Xu Chengyan,
Ding Wei,
Zhang Minmin,
Gu Yong
Publication year - 2013
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/nep.12146
Subject(s) - medicine , angiotensin receptor , kidney disease , angiotensin receptor blockers , angiotensin ii , renin–angiotensin system , pharmacology , disease , angiotensin ii receptor type 1 , receptor , endocrinology , blood pressure
Aim A ngiotensin‐(1–7) ( A ng‐(1–7)) opposes angiotensin‐ II ‐induced cell growth, matrix accumulation and fibrosis in cardiac tissue. However, the role of A ng‐(1–7) in the pathogenesis of renal fibrosis is uncertain. This study observed the effects of A ng‐(1–7), on its own or in combination with losartan, an angiotensin‐receptor blocker, on five‐sixths nephrectomized rats. Methods M ale S prague– D awley rats underwent five‐sixths nephrectomy, and then were either untreated, treated with A ng‐(1–7), treated with losartan, or treated with a combination therapy of A ng‐(1–7) and losartan. After 8 weeks, renal function was assessed by measuring systolic blood pressure, serum creatinine and proteinuria. The effect of nephrectomy on the renin–angiotensin system was examined by measuring plasma levels of A ng‐ II and A ng‐(1–7). The extent of glomerulosclerosis and tubulointerstitial fibrosis was assessed by periodic acid‐ S chiff staining and M asson‐trichrome staining. The expression of plasminogen activator inhibitor‐1, fibronectin and angiopoietins‐ T ie‐2 was investigated by immunohistochemistry and western blot. Results In the groups of treated rats, serum creatinine, proteinuria and markers of glomerulosclerosis, such as fibronectin and plasminogen activator inhibitor‐1, were ameliorated compared with the untreated, nephrectomized rats. Plasma A ng‐(1–7) levels were elevated in all treatment groups, but the plasma A ng‐ II levels were reduced in the A ng‐(1–7)‐treated group and the combination therapy group. The ratio of A ng‐1/ A ng‐2 was increased in the combination therapy group compared with two other treatment groups. Conclusion A ng‐(1–7) ameliorated the renal injury of nephrectomized rats. The combination of A ng‐(1–7) treatment alongside losartan exerted a superior effect to that of A ng‐(1–7) alone on regression of glomerulosclerosis.