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Role of proteinuria in the regulation of renal renin-angiotensin system components in unilateral proteinuric rats

Department of Clinical Pharmacology, Groningen University Institute for Drug Exploration, University of Groningen, Groningen, The Netherlands, l.e.deelman{at}med.rug.nl

Gerjan Navis

Department of Nephrology, University Hospital, Groningen, The Netherlands

Erik de Boer

Department of Nephrology, University Hospital, Groningen, The Netherlands

Mirian Wietses

Department of Clinical Pharmacology, Groningen University Institute for Drug Exploration, University of Groningen, Groningen, The Netherlands

Dick de Zeeuw

Department of Clinical Pharmacology, Groningen University Institute for Drug Exploration, University of Groningen, Groningen, The Netherlands

Robert H Henning

Department of Clinical Pharmacology, Groningen University Institute for Drug Exploration, University of Groningen, Groningen, The Netherlands

Renin-angiotensin system (RAS) overactivity has been implied in progressive renal function loss. We investigated whether changes in the renal expression of RAS components are specifically associated with the proteinuric kidney.

Unilateral adriamycin-induced proteinuria was obtained by clamping the left renal artery before injection of adriamycin. In control animals, both left and right renal arteries were clamped. Twelve weeks later, mRNA expression of RAS components was determined in both kidneys. In the affected and non-affected kidney of the unilateral proteinuric rat, we demonstrate up-regulation of angiotensin-converting enzyme (ACE) mRNA (213%±22 and 188%±24 of controls, respectively), up-regulation of transforming growth factor (TGF- ) mRNA (956%±229 and 418%±56) and down-regulation of angiotensin type 2 receptor (AT₂-R) mRNA (24%±5 and 20%±5). The expression of angiotensin type 1 receptor (AT₁-R) mRNA and inositol 1,4,5-trisphosphate receptor type I (IP₃R-I) mRNA were unchanged.

In conclusion, renal expression of ACE, AT₂-R, and AT₁-R mRNA is not mediated by protein leakage. Local intrarenal protein leakage did influence renal TGF- mRNA expression.

Key Words: adriamycin • rats • angiotensin • ACE • transforming growth factor ß

Journal of Renin-Angiotensin-Aldosterone System, Vol. 4, No. 1, 38-42 (2003)
DOI: 10.3317/jraas.2003.006


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