Korean J Med.  2004 Dec;67(6):615-624.

The anti-inflammatory effects of angiotensin II blockade in animal model of cyclosporine-induced nephropathy

• Song JC
• Shin MJ
• Jun YJ
• Woo SY
• Hyoung BJ
• Yoon HE
• Woo HY
• Choi BS
• Yang CW
• Kim YS
• Chang YS
• Bang BK

Abstract

BACKGROUND: Long-term treatment of immunosuppresant CsA causes interstitial inflammation and fibrosis in the kidney. Renin-angiotensin system (RAS) plays the most important role in the pathogenesis CsA-induced renal injury. Accordingly we evaluated the anti-inflammatory effect of angiotensin II blockades using losartan (LSRT) in a rat model of chronic CsA nephropathy.
METHODS
Male Sprague-Dawley rats, initially weighing 225 to 250 g, were used. After 1 week of a low-salt diet (0.05% sodium), the rats were randomized into four groups and treated for 4 weeks. The Vehicle (VH) group was treated with olive oil. The VH+LSRT group was treated with olive oil and LSRT. The CsA group received CsA. The CsA+LSRT group was simultaneously treated with CsA and LSRT. The anti-inflammatory effect of LSRT was evaluated with C-reactive protein (CRP) expression, osteopontin (OPN) mRNA and protein expression, and ED-1 infiltration
RESULTS
The CsA treatment caused an increase in serum creatinine and a decrease in creatinine clearance compared with that of the VH group. Intrarenal CRP positive cells were significantly decreased in the CsA+LSRT group compared with the CsA group (38.0 +/- 2.1 vs. 65.0 +/- 5.1, p<0.01). In the CsA group, the degree of OPN mRNA expression was increased compared with that of the VH group. But, OPN mRNA expression was decreased in the CsA+LSRT group (387.5 +/- 56.6% vs. 719.8 +/- 58.5%, p<0.05). In the degree of ED-1 infiltration, we had a similar results such as CRP and OPN mRNA expression (CsA group 30.5 +/- 8.0 vs. CsA+LSRT 86.0 +/- 11.0, p<0.01).
CONCLUSION
We concluded that the anti-inflammatory effects of angiotensin II blockade has a potential protective effect against CsA-induced renal injury.

Keyword

Cyclosporine nephropathy; Angiotensin II blockade; C-reactive protein; Osteopontin; ED-1

MeSH Terms

Angiotensin II*
Angiotensins*
Animals*
C-Reactive Protein
Creatinine
Diet, Sodium-Restricted
Fibrosis
Humans
Inflammation
Kidney
Losartan
Male
Models, Animal*
Olea
Osteopontin
Rats
Rats, Sprague-Dawley
Renin-Angiotensin System
RNA, Messenger
Olive Oil
Angiotensin II
Angiotensins
C-Reactive Protein
Creatinine
Losartan
Osteopontin
RNA, Messenger