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.
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate; D006439:Hemodynamics; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007472:Iohexol / Q000378:metabolism; D007511:Ischemia; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D008297:Male; D008833:Microcirculation; D009569:Nitric Oxide / Q000378:metabolism; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury; D019821:Simvastatin / Q000494:pharmacology*; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D007472:Iohexol; D016572:Cyclosporine; D019821:Simvastatin; D006903:Hydroxymethylglutaryl CoA Reductases