Simvastatin attenuates renal ischemia/reperfusion injury in rats administered cyclosporine A

Background: 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors increase renal blood flow independent of their lipid-lowering properties. In organ transplantation, the calcineurin inhibitor cyclosporine A (CyA) is the immunosuppressant of choice. However, its renal vasoconstrictor properties limit its use. This study aimed to determine the effect of an HMG-CoA reductase inhibitor, simvastatin (Zocor), on renal function in rats after ischemia/reperfusion injury (I/R) with concomitant CyA treatment. Methods: Male Wistar rats (250 g) were anesthetized and the suprarenal aorta clamped for 40 minutes. The right kidney was removed. After recovery, the rats were divided into 5 groups: (1) control rats, no ischemia, no treatment; (2) ischemia with no treatment; (3) ischemia plus CyA only; (4) ischemia plus CyA and low-dose simvastatin; and (5) ischemia plus CyA and high-dose simvastatin. Five to 7 days after I/R injury, glomerular filtration rate (GFR) was determined using urinary iohexol clearance. Results: The GFR values (mL/min) for all 5 groups were as follows: (1) 1.23 +/- 0.08; (2) 1.05 +/- 0.10; (3) 0.44 +/- 0.06 (P < 0.05 versus groups 1, 2, and 5; one-way analysis of variance); (4) 0.51 +/- 0.04 (P < 0.05 versus groups 1, 2, and 5; one-way analysis of variance); and (5) 0.85 +/- 0.11. Conclusions: After I/R injury and cyclosporine treatment, simvastatin preserved renal function compared with cyclosporine treatment alone because it may not have a direct vasoconstrictor effect on the renal microcirculation. In fact, it may exhibit vasodilator properties on the renal microcirculation mediated by nitric oxide.