This Article Free Full Text (Free PDF) Free References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Bos, H. Articles by Navis, G. Search for Related Content PubMed PubMed Citation Articles by Bos, H. Articles by Navis, G. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB DOXORUBICIN Social Bookmarking                         What's this?

Involvement of renal ACE activity in proteinuria-associated renal damage in untreated and treated adriamycin nephrotic rats

Departments of Clinical Pharmacology, Department of Nephrology, University of Groningen

Gozewijn D Laverman

Department of Nephrology, University of Groningen

Robert H Henning

Departments of Clinical Pharmacology

Anton TMG Tiebosch

Department of Pathology, Faculty of Medical Sciences and Groningen University Institute of Drug Exploration (GUIDE), University of Groningen, Groningen, The Netherlands

Paul E de Jong

Department of Nephrology, University of Groningen

Dick de Zeeuw

Departments of Clinical Pharmacology, Department of Nephrology, University of Groningen

Gerjan Navis

Departments of Clinical Pharmacology, Department of Nephrology, University of Groningen, g.j.navis@ int.azg.nl

Proteinuria is assumed to play a pathogenetic role in progressive renal damage. Angiotensin-converting enzyme (ACE) inhibition reduces proteinuria and provides renoprotection. This suggests that ACE activity might play a pathogenetic role in the development of proteinuria-induced renal structural damage. We investigated this hypothesis in untreated and treated established adriamycin nephrosis, a model of proteinuria-induced renal damage.

In a time-course experiment, the development of renal structural damage in untreated adriamycin nephrotic rats was paralleled by a significant rise in renal ACE activity. Moreover, on cross-sectional analysis, a consistent positive correlation between renal, but not plasma, ACE activity and proteinuria, focal glomerulosclerosis and interstitial injury was present. Notably, these associations were present, not only in the untreated condition, but also during intervention with either ACE inhibition or AT₁-receptor antagonism. Interestingly, we found that higher renal ACE activity is associated with more severe renal damage for a given amount of proteinuria, suggesting that renal ACE activity may be either a permissive or a promoting factor in the processes by which proteinuria eventually leads to renal structural damage. This relationship was abolished by renin-angiotensin system (RAS)-blockade, suggesting that RAS-mediated effects are involved in the relationship between renal ACE activity and proteinuria-induced renal damage.

In conclusion, in untreated as well as treated adriamycin nephrotic rats, renal ACE activity is closely associated with renal outcome. This association appears to be independent of the specific mode of blockade of the RAS. Renal ACE activity is a consistent marker of individual differences in proteinuria-associated renal damage: further studies are needed to investigate a possible pathogenetic role in renal damage.

Key Words: renal ACE • proteinuria • treatment • ACE inhibition

Journal of Renin-Angiotensin-Aldosterone System, Vol. 4, No. 2, 106-112 (2003)
DOI: 10.3317/jraas.2003.010


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				I. Hamming, H. van Goor, A. J. Turner, C. A. Rushworth, A. A. Michaud, P. Corvol, and G. Navis Differential regulation of renal angiotensin-converting enzyme (ACE) and ACE2 during ACE inhibition and dietary sodium restriction in healthy rats Exp Physiol, May 1, 2008; 93(5): 631 - 638. [Abstract] [Full Text] [PDF]

				A. Kramer, M. van den Hoven, A. Rops, T. Wijnhoven, L. van den Heuvel, J. Lensen, T. van Kuppevelt, H. van Goor, J. van der Vlag, G. Navis, et al. Induction of Glomerular Heparanase Expression in Rats with Adriamycin Nephropathy Is Regulated by Reactive Oxygen Species and the Renin-Angiotensin System J. Am. Soc. Nephrol., September 1, 2006; 17(9): 2513 - 2520. [Abstract] [Full Text] [PDF]