TY - JOUR
T1 - Pathological expression of renin and angiotensin II in the renal tubule after subtotal nephrectomy
T2 - Implications for the pathogenesis of tubulointerstitial fibrosis
AU - Gilbert, Richard E.
AU - Wu, Leonard L.
AU - Kelly, Darren J.
AU - Cox, Alison
AU - Wilkinson-Berka, Jennifer L.
AU - Johnston, Colin I.
AU - Cooper, Mark E.
PY - 1999
Y1 - 1999
N2 - The finding that the systemic renin-angiotensin system (RAS) is not activated 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 progression of renal disease. Therefore, cell specific changes in various components of the RAS in response to renal mass reduction and angiotensin converting enzyme (ACE) inhibition were examined. Thirty Sprague- Dawley rats were randomly assigned to sham surgery, subtotal nephrectomy (STNx) alone or STNx treated with the ACE inhibitor, perindopril, and sacrificed after 12 weeks. In sham rats, renin mRNA and protein were only present in the juxtaglomerular apparatus. In contrast, in STNx kidneys, renin and angiotensin II expression were noted predominantly in renal tubular epithelial cells in association with overexpression of the prosclerotic cytokine, transforming growth factor-β1 (TGF-β1). In perindopril-treated STNx rats expression of renin and TGF-β1 were similar to control animals. These finding indicate that following renal mass reduction there is pathological tubular expression of various components of the RAS. Furthermore, in contrast to the juxtaglomerular apparatus, tubular renin expression was reduced with ACE inhibition. These changes within the intrarenal RAS may be pathogenetically linked to the development of tubulointerstitial injury.
AB - The finding that the systemic renin-angiotensin system (RAS) is not activated 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 progression of renal disease. Therefore, cell specific changes in various components of the RAS in response to renal mass reduction and angiotensin converting enzyme (ACE) inhibition were examined. Thirty Sprague- Dawley rats were randomly assigned to sham surgery, subtotal nephrectomy (STNx) alone or STNx treated with the ACE inhibitor, perindopril, and sacrificed after 12 weeks. In sham rats, renin mRNA and protein were only present in the juxtaglomerular apparatus. In contrast, in STNx kidneys, renin and angiotensin II expression were noted predominantly in renal tubular epithelial cells in association with overexpression of the prosclerotic cytokine, transforming growth factor-β1 (TGF-β1). In perindopril-treated STNx rats expression of renin and TGF-β1 were similar to control animals. These finding indicate that following renal mass reduction there is pathological tubular expression of various components of the RAS. Furthermore, in contrast to the juxtaglomerular apparatus, tubular renin expression was reduced with ACE inhibition. These changes within the intrarenal RAS may be pathogenetically linked to the development of tubulointerstitial injury.
UR - http://www.scopus.com/inward/record.url?scp=0032814167&partnerID=8YFLogxK
M3 - Article
C2 - 10433936
AN - SCOPUS:0032814167
VL - 155
SP - 429
EP - 440
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 2
ER -