ABSTRACT
The present study was aimed at investigating the effect of cyclosporine A (CsA) on the renal renin-angiotensin systems. In rats chronically treated with CsA, the intrarenal expression of various genes of the renin-angiotensin system was assessed by Northern blot analysis. Along with the increases in plasma and renal renin activities, chronic CsA-treatment differentially affected the renal expression of renin-angiotensin system. The treatment with CsA for one week did not significantly alter the expression of either type 1 angiotensin II receptor (AT1A) or angiotensinogen gene, but increased the renin mRNA level. The three-week-treatment caused increases in the expression not only of renin but also of AT1A and angiotensinogen genes. Supplementation with L-arginine kept the expression of renin mRNA normal in the one-week-treated, but failed to prevent the alterations of the gene expression in the three-week-treated. Feedback control among components of the renin-angiotensin system also influences angiotesinogen. In the liver, the expression of angiotensinogen mRNA was decreased by the CsA-treatment for either one- or three-weeks. In conclusion, chronic CsA-treatment is associated with a differential expression of various genes for the renin-angiotensin system. L-Arginine may be effective in maintaining the normality of renin-angiotensin system only during early period after beginning the use of CsA.