Role of proteinuria in the regulation of renal renin-angiotensin system components in unilateral proteinuric rats.
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 beta (TGF-beta) 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-beta mRNA expression.
Deelman
Leo E
LE
Department of Clinical Pharmacology, University of Groningen, Groningen, 9713AV, The Netherlands.
Navis
Gerjan
G
de Boer
Erik
E
Wietses
Mirian
M
de Zeeuw
Dick
D
Henning
Robert H
RH
D000818:Animals; D000970:Antineoplastic Agents; D001794:Blood Pressure; D015220:Calcium Channels / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D004317:Doxorubicin; D015870:Gene Expression / Q000502:physiology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007668:Kidney / Q000254:growth & development / Q000502:physiology*; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000401:mortality / Q000503:physiopathology*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011507:Proteinuria / Q000139:chemically induced / Q000401:mortality / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D012084:Renin-Angiotensin System / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics
D000970:Antineoplastic Agents; D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D018160:Receptors, Cytoplasmic and Nuclear; D016212:Transforming Growth Factor beta; D004317:Doxorubicin; D002784:Cholesterol; D007703:Peptidyl-Dipeptidase A