Nicorandil ameliorates ischaemia-reperfusion injury in the rat kidney.
OBJECTIVE
Nicorandil, an ATP-sensitive potassium (K(ATP) ) channel opener and nitric oxide donor, is used in the treatment of angina and acute heart failure. Here we investigated the effects of two K(ATP) channel openers, nicorandil and cromakalim on ischaemia reperfusion (I-R) injury in the kidney.


METHODS
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 K(ATP) channel subtypes were investigated by Western blot. Kidney sections were stained for 4-hydroxy-2-nonenal and 8-hydroxy-2'-deoxyguanosine.


RESULTS
Renal I-R induced significant increases in SCr, ACR and β2-MG levels compared with the control animals. Treatment with K(ATP) channel openers reduced urinary β2-MG levels, raised by I-R. Both K(IR) 6.1 and K(IR) 6.2 channels were expressed. Expression of K(IR) 6.2 channels in the I-R group was lower than in the control group, which was restored to normal by treatment with K(ATP) channel openers. Histologically, severe acute tubular damage was observed in the I-R kidney and this damage was ameliorated by K(ATP) channel openers, dose-dependently.


CONCLUSIONS
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.
Division of Molecular Pharmacology, Tottori University School of Medicine, Yonago, Japan.
Shogo
S
Shimizu
Motoaki
M
Saito
Yukako
Y
Kinoshita
Fumiya
F
Ohmasa
Fotios
F
Dimitriadis
Kohei
K
Shomori
Atsushi
A
Hayashi
Keisuke
K
Satoh
D000818:Animals; D019806:Cromakalim / Q000494:pharmacology / Q000627:therapeutic use; D004249:DNA Damage; D015640:Ion Channel Gating; D054086:KATP Channels / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000473:pathology; D015227:Lipid Peroxidation; D008297:Male; D020108:Nicorandil / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D000099161:Kcnj11 Channel
D019806:Cromakalim; D054086:KATP Channels; D020108:Nicorandil; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel; C092520:uK-ATP-1 potassium channel
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