Failure of Verapamil to Protect from Ischaemic Renal Damage

Abstract

To reassess the reported protective effects of verapamil in renal ischaemia, we perfused the left kidney of uninephrectomized female Wistar rats with verapamil (0.1 and 1.0 mg/kg) immediately prior to clamping the renal artery for 60 min. When compared to controls, both doses of verapamil failed to afford protection with respect to urine flow, plasma creatinine, creatinine clearance or histology 24 and 48 h after ischaemia, whereas the purine nucleotide inosine (200 mg/kg) was partially protective: mean plasma creatinine 48 h after ischaemia (+/- SEM) was 547 +/- 54 mumol/l in controls, 686 +/- 38 mumol/l with 0.1 mg/kg verapamil, 491 +/- 68 mumol/l with 1.0 mg/kg verapamil and 374 +/- 45 mumol/l with inosine (p less than 0.05 vs. controls). Using the same model, the effect of verapamil 1.0 mg/kg on renal blood flow, creatinine clearance, urine flow and arterial pressure was studied in the first 2 h after ischaemia. Although significant amounts of verapamil were present in the kidney during ischaemia as evidenced by decreases in systemic blood pressure and in renal vascular resistance after unclamping the renal artery, the early course of renal failure was not altered when compared to controls. In conclusion, we have been unable to confirm earlier reports of a protective effect of verapamil in this rat model of ischaemic renal failure. If there is such an effect, its demonstration appears to depend on very specific experimental circumstances. Based on the results of this and other studies, verapamil is unlikely to afford an impressive overall benefit in the clinical setting of ischaemic renal failure.