Nicorandil ameliorates ischaemia‐reperfusion injury in the rat kidney

BACKGROUND AND PURPOSE Nicorandil, an ATP‐sensitive potassium (KATP) channel opener and nitric oxide donor, is used in the treatment of angina and acute heart failure. Here we investigated the effects of two KATP channel openers, nicorandil and cromakalim on ischaemia reperfusion (I‐R) injury in the kidney. EXPERIMENTAL APPROACH Right nephrectomy was performed in 8‐week‐old male Sprague‐Dawley rats and they were then divided into six groups: control group; I‐R, including 30 min of left renal ischaemia followed by 24 h of reperfusion; I‐R groups plus nicorandil 3 or 10 mg·kg−1 i.p.; and I‐R groups plus cromakalim 100 or 300 µg·kg−1 i.p. After reperfusion, renal function was estimated by serum creatinine (SCr), urinary albumin : creatinine ratio (ACR) and urinary β2‐microglobulin (β2‐MG). Levels of KATP channel subtypes were investigated by Western blot. Kidney sections were stained for 4‐hydroxy‐2‐nonenal and 8‐hydroxy‐2′‐deoxyguanosine. KEY RESULTS Renal I‐R induced significant increases in SCr, ACR and β2‐MG levels compared with the control animals. Treatment with KATP channel openers reduced urinary β2‐MG levels, raised by I‐R. Both KIR6.1 and KIR6.2 channels were expressed. Expression of KIR6.2 channels in the I‐R group was lower than in the control group, which was restored to normal by treatment with KATP channel openers. Histologically, severe acute tubular damage was observed in the I‐R kidney and this damage was ameliorated by KATP channel openers, dose‐dependently. CONCLUSIONS AND IMPLICATIONS ATP‐sensitive potassium channel openers protected against proximal tubule damage after I‐R injury. Nicorandil could represent a powerful additional component in the treatment of patients undergoing partial nephrectomy or renal transplantation.