Intrarenal renin-angiotensin system is upregulated in experimental model of progressive renal disease induced by chronic inhibition of nitric oxide synthesis

Intrarenal renin-angiotensin system is upregulated in experimental model of progressive renal disease induced by chronic inhibition of nitric oxide synthesis

Author Graciano, M. L. Google Scholar
Cavaglieri, R. D. Google Scholar
Delle, H. Google Scholar
Dominguez, W. V. Google Scholar
Casarini, D. E. Google Scholar
Malheiros, DMAC Google Scholar
Noronha, I. L. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Abstract Locally generated angiotensin II (AngII) may be involved in the pathogenic mechanisms of chronic renal diseases. Renal expression of AngII and other components of the renin-angiotensin system (RAS) were analyzed by immunohistochemistry and Western blot in a model of chronic progressive nephropathy induced by inhibition of nitric oxide synthesis. Renal injury was evaluated by histology and albumin excretion. Systemic RAS status was evaluated through plasma renin activity (PRA) and plasma AngII concentration. in addition, the effects of enalapril, losartan, and mycophenolate mofetil (MMF) on AngII expression in animals with chronic renal disease was also analyzed. Plasma renin activity and plasma AngII were not different between rats with nephropathy and controls (2.08 +/- 0.7 versus 2.03 +/- 0.5 ng/ml/h and 94.3 +/- 18 versus 78.9 +/- 16 fmol/ml, respectively). However, rats with chronic progressive nephropathy showed augmented renal content of angiotensinogen protein (13.5 +/- 3.5 versus 2.2 +/- 0.4 pixels in control rats; P < 0.05), enhanced expression of cathepsin D-a renin-like enzyme-in cortical collecting tubules (103.5 +/- 27.0 versus 66.2 +/- 3.6 cells/mm(2) in controls; P < 0.01), and increased expression of AT, receptor in interstitium (54.7 +/- 7.8 versus 1.3 +/- 0.4 cells/mm(2) in controls; P < 0.001). Kidney angiotensin-converting enzyme content did not differ among the groups. Notably, an increased number of interstitial cells expressing AngII was detected in the renal interstitium (9.5 +/- 1.6 versus 1.7 +/- 0.6 cells/mm(2) in controls; P < 0.05). Rats treated with Nomega-nitro-L-arginine-methyl-esther and losartan presented a decreased local AngII formation, in contrast to its known effect on plasma AngII. Moreover, mycophenolate mofetil lowered interstitial AngII expression, suggesting that inflammatory signaling may be involved in interstitial AngII generation. This study demonstrates the upregulation of local RAS in the kidney in a model of chronic progressive nephropathy.
Language English
Date 2004-07-01
Published in Journal of the American Society of Nephrology. Philadelphia: Lippincott Williams & Wilkins, v. 15, n. 7, p. 1805-1815, 2004.
ISSN 1046-6673 (Sherpa/Romeo, impact factor)
Publisher Lippincott Williams & Wilkins
Extent 1805-1815
Origin http://dx.doi.org/10.1097/01.ASN.00000131528.00773.A9
Access rights Closed access
Type Article
Web of Science ID WOS:000222275600015
URI http://repositorio.unifesp.br/handle/11600/27830

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