ATP-dependent K+ channels in renal ischemia reperfusion injury.
ATP-dependent K+ channels (KATP) account for most of the recycling of K+ which enters the proximal tubules cell via Na, K-ATPase. In the mitochondrial membrane, opening of these channels preserves mitochondrial viability and matrix volume during ischemia. We examined KATP channel modulation in renal ischemia-reperfusion injury (IRI), using an isolated perfused rat kidney (IPRK) model, in control, IRI, IRI+200 microM diazoxide (a KATP opener), IRI + 10 microM glibenclamide (a KATP blocker) and IRI + 200 microM diazoxide + 10 microM glibenclamide groups. IRI was induced by 2 periods of warm ischemia, followed by 45 min of reperfusion. IRI significantly decreased glomerular filtration rate (GFR) and increased fractional excretion of sodium (FENa) (p < 0.01). Neither diazoxide nor glibenclamide had an effect on control kidney function other than an increase in renal vascular resistance produced by glibenclamide. Pretreatment with 200 microM diazoxide reduced the postischemic increase in FENa (p < 0.05). Adding 10 microM glibenclamide inhibited the diazoxide effect on postischemic FENa (p < 0.01). Histology showed that kidneys pretreated with glibenclamide demonstrated an increase in injury in the thick ascending limb of outer medulla (p < 0.05). Glibenclamide significantly decreased post ischemic renal vascular resistance (p < 0.05), but had no significant effect on other renal function parameters. Our results suggest that sodium reabsorption is improved by KATP activation and blockade of KATP channels during IRI has an injury enhancing effect on renal epithelial function and histology. This may be mediated through KATP modulation in cell and/or mitochondrial inner membrane.
Rahgozar
Majid
M
Department of Medicine, Central Clinical Division, School of Medicine, University of Queensland, Brisbane, Australia.
Willgoss
Desley A
DA
Gobé
Glenda C
GC
Endre
Zoltán H
ZH
D058186:Acute Kidney Injury / Q000188:drug therapy / Q000473:pathology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D019806:Cromakalim / Q000494:pharmacology*; D003981:Diazoxide / Q000494:pharmacology*; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D009924:Organ Culture Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011336:Probability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology*; D012680:Sensitivity and Specificity
D015221:Potassium Channels; D019806:Cromakalim; D000255:Adenosine Triphosphate; D003981:Diazoxide; D005905:Glyburide