Inhibition of ATP-activated potassium channels exerts pressor effects and improves survival in a rat model of severe hemorrhagic shock.
Potassium channels closed by increases in intracellular ATP levels (KATP channels) have been described in vascular smooth muscle cells and other cell types. These channels are responsive to the metabolic state of the cells, and can be opened by a decrease in intracellular ATP levels and intra- or extracellular acidosis. Hemorrhagic shock is associated with early vasomotor paralysis as well as with early derangements in the intracellular metabolic status. Here we have tested whether activation of KATP channels contributes to the vasodilatation and early mortality in a rat model of severe hemorrhagic shock. In anesthetized rats hemorrhaged to a mean arterial blood pressure (MAP) of 35 mmHg, inhibition of KATP channels with glibenclamide or tolazamide (10 mg/kg i.v. bolus injection followed by an infusion of 10 mg/kg/h for 60 min), rapidly increased MAP and improved survival rate. The same dose of the KATP channel inhibitors did not cause a significant increase of MAP in animals not subjected to hemorrhage. The approach of inhibition of KATP channel activation in hemorrhagic shock is worthy of further investigations to determine whether it may represent a novel approach for early resuscitation during hemorrhage.
Szabó
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Children's Hospital Medical Center, Division of Critical Care, Cincinnati, Ohio 45229, USA.
Salzman
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D018528:ATP-Binding Cassette Transporters; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D005905:Glyburide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology; D054086:KATP Channels; D008297:Male; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017208:Rats, Wistar; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D014042:Tolazamide / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D054086:KATP Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D006493:Heparin; D014042:Tolazamide; D005905:Glyburide