Protective effects of angiotensin-(1-7) administrated with an angiotensin-receptor blocker in a rat model of chronic kidney disease

摘要

Aim: Angiotensin-(1-7) (Ang-(1-7)) opposes angiotensin-II-induced cell growth, matrix accumulation and fibrosis in cardiac tissue. However, the role of Ang-(1-7) in the pathogenesis of renal fibrosis is uncertain. This study observed the effects of Ang-(1-7), on its own or in combination with losartan, an angiotensin-receptor blocker, on five-sixths nephrectomized rats. Methods: Male Sprague-Dawley rats underwent five-sixths nephrectomy, and then were either untreated, treated with Ang-(1-7), treated with losartan, or treated with a combination therapy of Ang-(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 Ang-II and Ang-(1-7). The extent of glomerulosclerosis and tubulointerstitial fibrosis was assessed by periodic acid-Schiff staining and Masson-trichrome staining. The expression of plasminogen activator inhibitor-1, fibronectin and angiopoietins-Tie-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 Ang-(1-7) levels were elevated in all treatment groups, but the plasma Ang-II levels were reduced in the Ang-(1-7)-treated group and the combination therapy group. The ratio of Ang-1/Ang-2 was increased in the combination therapy group compared with two other treatment groups. Conclusion: Ang-(1-7) ameliorated the renal injury of nephrectomized rats. The combination of Ang-(1-7) treatment alongside losartan exerted a superior effect to that of Ang-(1-7) alone on regression of glomerulosclerosis.