Pathological expression of renin and angiotensin II in the renal tubule after subtotal nephrectomy - Implications for the pathogenesis of tubulointerstitial fibrosis

The finding that the systemic renin-angiotensin system (RAS) is not activat ed in most types of chronic renal disease has led to the suggestion that a local, intrarenal RAS may be an important determinant in the relentless pro gression of renal disease. Therefore, cell specific changes in various comp onents of the RAS in response to renal mass reduction and angiotensin conve rting enzyme (ACE) inhibition were examined. Thirty Sprague-Dawley rats mer e randomly assigned to sham surgery, subtotal nephrectomy (STNx) alone or S TNx treated with the ACE inhibitor, perindopril, and sacrificed after 12 we eks, In sham rats, renin mRNA and protein were only present in the juxtaglo merular apparatus, In contrast, in STNx kidneys, renin and angiotensin II e xpression mere noted predominantly in renal tubular epithelial cells in ass ociation with overexpression of the prosclerotic cytokine, transforming gro wth factor-beta 1 (TGF-beta 1), In perindopril-treated STNx rats expression of renin and TGF-beta 1 were similar to control animals. These finding ind icate that following renal mass reduction there is pathological tubular exp ression of various components of the RAS, Furthermore, in contrast to the j uxtaglomerular apparatus, tubular renin expression was reduced with. ACE in hibition. These changes within the intrarenal RAS may be pathogenetically L inked to the development of tubulointerstitial injury.