The role of ATP-sensitive potassium channel blockers in ischemia-reperfusion-induced renal injury versus their effects on cardiac ischemia reperfusion in rats

Mona K. Tawfik°, Dina M. Abo-ElMatty*°, Amal A.M. Ahmed**°

Department of Pharmacology, Faculty of Medicine, *Department of Biochemistry, Faculty of Pharmacy, **Department of Histology, Faculty of Veterinary Medicine, °Suez Canal University, Ismailia (Egypt)

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• Pharmacology

In renal ischemia reperfusion (I/R), opening of adenosine-triphosphate (ATP)-sensitive potassium (KATP) channels results in massive influx of neutrophils in both renal and lung tissues. Our study was focused on the role of ATP-dependent potassium channel modulators, glimepiride and glibenclamide on I/R induced renal injury in rats. Additionally we evaluated their effects on normal heart and on ischemic reperfused heart subjected to ischemic preconditioning protection afforded by diazoxide. To test this hypothesis, we used renal I/R and cardiac I/R experiment. Renal ischemia reperfusion induced marked renal dysfunction associated with significant increase in arterial pressure, TNF-alpha levels, superoxide anion production, and myeloperoxidase activity. Treatment with glibenclamide or glimepiride, demonstrated a significant improvement in the reperfusion-induced injury in both kidney and lung. Glimepiride has no effect on superoxide anion production. However glibenclamide induced a significant improvement in these measurements as compared to glimepiride group.
Before coronary artery ligation, neither diazoxide nor glimepiride pretreatment influenced significantly the electrocardiographic parameters in comparison with control group. Conversely, glibenclamide supplementation induced a significant elevation in these parameters. After left coronary artery ligation, reperfusion of the ischemic hearts caused a significant elevation in the measured electrocardiographic parameters. These elevations were significantly ameliorated by the pretreatment with diazoxide. In conclusion, the administration of glibenclamide significantly abolished the protective effects of diazoxide, while the pretreatment with glimepiride didn’t abolish it. So, glimepiride offers some promise for therapy of renal I/R with minimizing the undesirable cardiac side effects.

Corresponding Author: Mona K. Tawfik, MD; e-mail: dmon_kamal@yahoo.com

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