possible renoprotective effect of angiotensin converting enzyme inhibitors and statins on renal ischemia reperfusion injury in rats

ABSTRACT

Ischemia-reperfusion-induced renal injury is the most common cause of acute renal failure [ARF]. Angiogenesis is an important phenomenon associated with recovery from ischemia. The aim of the present study was to assess the possible renoprotective effect of manipulating angiogenesis by trandolapril [an angiotensin converting enzyme [ACE] inhibitor] and simvastatin [a 3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase inhibitor] in ischemic ARF in rat. The present study was conducted on 40 male albino rats that were divided into four groups. Group I included normal Sham-operated rats that served as control for group II, Group II were rats in which renal ischemia reperfusion injury [RIRI] was induced and Group III and Group IV consisted of rats that received trandolapril and simvastatin respectively, orally daily starting two days before and continuing for two days after the induction of RIRI. At the end of the experimental period, serum urea and creatinine concentrations and creatinine clearance were assessed. Moreover, serum and renal vascular endothelial growth factor [VEGF] levels, renal caspase-3 activity [as an index of apoptosis], renal hemoglobin content [as an index of angiogenesis] and renal oxidative stress parameters [malondialdhyde [MDA] and reduced glutathione [GSH] concentrations] were assessed. A significant increase in serum urea, creatinine concentrations and in renal VEGF, MDA concentrations and caspase-3 activity together with a significant decrease in creatinine clearance and renal GSH concentration has been observed in non-treated rats killed two days after RIRI compared to Sham-operated rats. Administration of trandolapril or simvastatin resulted in a significant decrease in serum urea and creatinine concentrations and in renal caspase-3 activity and renal MDA concentration as well as a significant increase in creatinine clearance and renal hemoglobin and GSH concentrations in rats killed two days following RIRI compared to non-treated rats with RIRI. A significant increase in renal VEGF concentration could be observed in simvastatin-, but not in trandolapril-treated rats killed two days following RIRI compared to non-treated rats with RIRI. The present study demonstrated the proangiogenic effect and the possible renoprotective role of trandolapril and simvastatin in rats with RIRI. It has been found that the proangiogenic effect of trandolapril is independent of VEGF, while that of simvastatin might involve several factors including VEGF