[Role of activation of renin angiotensin system in cyclosporine A nephropathy].
OBJECTIVE
To investigate the role of renin angiotensin system (RAS) activation in cyclosporine A nephropathy.


METHODS
Rats were fed with low salt diet. After seven days, they were randomly divided into four groups: vehicle (n=7), CsA treated (n=7), CsA+verapamil (n=7), CsA+enalapril (n=7). All rats except vehicle received a daily subcutaneous injection of CsA (15 mg/kg) for four weeks. Plasma and renal tissue angiotensin II (Ang II) levels were measured by radioimmunoassay. The expression of angiotensin II type 1 receptor (AT1R) was examined by Northern blot.


RESULTS
Plasma and renal tissue angiotensin II levels were significantly elevated in CsA treated rats when compared to that in vehicle rats ((190+/-36)ng/L vs. (492+/-92)ng/L, (29.8+/-6.0)ng/g vs. (8.7+/-1.7) ng/g, P<0.001). Enalapril reduced angiotensin II levels significantly (both P<0.05). The expression of AT1R mRNA was down-regulated by CsA, this down-regulation was reversed by enalapril. CsA treated animals showed marked tubulointerstitial fibrosis, enalapril lessened the tubulointerstitial fibrosis significantly (P<0.05). Verapamil did not improve tubulointerstitial fibrosis significantly (P>0.05).


CONCLUSIONS
RAS activation plays an important part in CsA nephropathy. Blockade of RAS may retard the progression of tubulointerstitial fibrosis caused by CsA.
Zhang
Guo-hua
GH
Department of Nephrology, Nanfang Hospital, The First Military Medical University, Guangzhou 510515, Guangdong, China.
Zhang
Xun
X
Hou
Fan-fan
FF
Wang
Li
L
D000804:Angiotensin II / Q000032:analysis; D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D016572:Cyclosporine