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 (K_ATP 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 K_ATP 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 K_ATP 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 K_ATP channel inhibitors did not cause a significant increase of MAP in animals not subjected to hemorrhage. The approach of inhibition of K_ATP channel activation in hemorrhagic shock is worthy of further investigations to determine whether it may represent a novel approach for early resuscitation during hemorrhage.