Prevention of experimental cyclosporin-induced interstitial fibrosis by losartan and enalapril

Emmanuel A. Burdmann, Takeshi F. Andoh, Cynthia C. Nast, Andrew Evan, Bret A. Connors, Thomas M. Coffman, Jessie Lindsley, William M. Bennett

Research output: Contribution to journalArticlepeer-review

166 Scopus citations


The pathogenesis of renal scarring in chronic cyclosporin nephropathy is unknown. In this study, we evaluated the effects of renin-angiotensin system blockade by enalapril and losartan in a salt-dependent model of cyclosporin-associated chronic tubulointerstitial fibrosis (TIF). Rats kept on normal or low-salt diet were given cyclosporin, cyclosporin + enalapril, cyclosporin + losartan, cyclosporin + enalapril + losartan, or vehicle for 14 and 28 days. Cyclosporin reduced glomerular filtration rate (GFR) in rats fed either diet, but only salt-depleted animals developed significant TIF. Cyclosporin also impaired renal concentrating ability and caused tubular enzymuria. Renin-angiotensin system blockade decreased blood pressure (BP) and promoted afferent arteriolar vasodilatation. Losartan reduced plasma renin activity and prevented cyclosporin-induced increment of cortical α1(I) procollagen mRNA. Renin-angiotensin blockade did not improve GFR and tubular function; however, it strikingly prevented TIF development, even in presence of very low BP. Rats treated with cyclosporin, hydralazine, and furosemide achieved BP values similar to losartan or enalapril groups, but there was no protection against interstitial fibrosis development. These results suggest that cyclosporin-related chronic interstitial injury is mediated by angiotensin II and that the mechanisms promoting the interstitial scarring can be dissociated from glomerular and tubular dysfunction in cyclosporin nephropathy.

Original languageEnglish (US)
Pages (from-to)F491-F499
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Issue number4 38-4
StatePublished - Oct 1995


  • Angiotensin II
  • Chronic nephrotoxicity
  • Rats
  • Renin

ASJC Scopus subject areas

  • Physiology


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