Prevention of diabetic nephropathy by compound 21, selective agonist of angiotensin type 2 receptors, in Zucker diabetic fatty rats

Giovanna Castoldi, Cira R T di Gioia, Camila Bombardi, Silvia Maestroni, Raffaella Carletti, U. Muscha Steckelings, Bjorn Dahlöf, Thomas Unger, Gianpaolo Zerbini, Andrea Stella

Research output: Contribution to journalArticle

Abstract

The aim of this study was to evaluate the effect of compound 21 (C21), a selective AT2 receptor agonist, on diabetic nephropathy and the potential additive effect of C21, when associated with losartan treatment, on the development of albuminuria and renal fibrosis in Zucker diabetic fatty (ZDF) rats. The experiments lasted 15 wk (from 5 to 20 wk of age) and were performed in 40 ZDF rats and 12 control lean rats. ZDF rats were divided into 4 groups: 1) 9 rats were treated with losartan; 2) 10 rats were treated with C21; 3) 9 rats were treated with losartan plus C21; and 4) 12 rats were maintained without any treatment. ZDF rats showed an increase in blood glucose level, albuminuria, renal fibrosis, macrophage infiltration, and TNF-α expression and a reduction of glomerular nephrin expression compared with control lean rats. C21 treatment reduced renal glomerular, tubulointerstitial, and perivascular fibrosis, and macrophage infiltration and TNF-α expression in ZDF rats. C21 treatment caused a decrease in albuminuria in ZDF rats up to 11 wk of age. Losartan decreased macrophage infiltration, TNF-α expression, and renal glomerular and perivascular fibrosis, restored glomerular nephrin expression, but did not affect tubulointerstitial fibrosis. Losartan treatment caused a decrease in albuminuria in ZDF rats up to 15 wk of age. At the end of the protocol, only the combination of C21 plus losartan significantly reduced albuminuria in ZDF rats. These data demonstrate that C21 has beneficial effects on diabetic nephropathy, suggesting the combination of C21 and losartan as a novel pharmacological tool to slow the progression of nephropathy in type II diabetes.

Original languageEnglish
Pages (from-to)F1123-F1131
JournalAmerican Journal of Physiology - Renal Physiology
Volume307
Issue number10
DOIs
Publication statusPublished - Nov 15 2014

Keywords

  • Compound 21
  • Diabetic nephropathy
  • Experimental models
  • Renal fibrosis
  • Urinary albumin excretion
  • Zucker diabetic fatty rats

ASJC Scopus subject areas

  • Physiology
  • Urology
  • Medicine(all)

Fingerprint Dive into the research topics of 'Prevention of diabetic nephropathy by compound 21, selective agonist of angiotensin type 2 receptors, in Zucker diabetic fatty rats'. Together they form a unique fingerprint.

  • Cite this

    Castoldi, G., di Gioia, C. R. T., Bombardi, C., Maestroni, S., Carletti, R., Steckelings, U. M., Dahlöf, B., Unger, T., Zerbini, G., & Stella, A. (2014). Prevention of diabetic nephropathy by compound 21, selective agonist of angiotensin type 2 receptors, in Zucker diabetic fatty rats. American Journal of Physiology - Renal Physiology, 307(10), F1123-F1131. https://doi.org/10.1152/ajprenal.00247.2014