Strain differences in angiotensin-converting enzyme and angiotensin II type I receptor expression. Possible implications for experimental chronic renal transplant failure

Background The Fisher to Lewis (F-L) model of renal transplantation (Rtx) is widely used. Rtx from F to L without immunosuppressive treatment results in 50% survival, whereas L to F results in survival rates similar to syngrafts. When treated with an angiotensin-converting enzyme (ACE) inhibitor or antihypertensive triple therapy, renal damage is markedly reduced in F-L allografts. Despite similar reductions in blood pressure, the ACE inhibitor (ACE-I) is more effective than antihypertensive triple therapy, suggesting that the inhibition of intrarenal ACE plays an additional role in the attenuation of renal damage.Methods In the present study, we investigated strain-related differences in intrarenal ACE activity between F and L rats and whether treatment with ACE-I in F-L allografted rats results in reduction of intrarenal ACE. Intrarenal ACE was measured by activity assays, immunohistochemistry and PCR.Results In control kidneys from healthy F rats (n=8), we found a four-fold higher ACE activity than in native L rats (n=8, pConclusion In conclusion, intrarenal levels of ACE may play a role in the development of renal damage in experimental chronic renal transplant failure.