Glyburide, a K+ATP channel blocker, improves hypotension and survival in anaphylactic shock induced in Wistar rats sensitized to ovalbumin

Abstract

Allergens can induce anaphylactic shock and death due to severe hypotension. Potassium channel blockers (K+ATP) such as glyburide (GLY) induce vasoconstriction. The effect of K+ATP channel blockers on anaphylactic shock is poorly understood. Objective of the study was to test the hypothesis that GLY reduces hypotension induced in anaphylactic shock and increases survival. Rats were grouped into: G1-N=Naïve; G2-SC=Sensitized-Control; G3-SG=Sensitized-GLY (glyburide 40mg/kg); G4-SE=Sensitized-EPI (epinephrine 10µg/kg). G2 to G4 groups were sensitized with ovalbumin (OVA) and shock was induced by i.v. injection of OVA. Treatments were administered intravenously 5min later. Mean arterial pressure (MAP), heart rate (HR), and mean survival time (MST) were measured for 60min following OVA injection and treatments administration. At the end of the experiment, blood withdrawal was performed to measure plasma levels of histamine, leukotriene B4 (LTB4), prostaglandin E2 (PGE2) and prostaglandin F2 (PGF2). Additionally blood gas (paO2, paCO2, SaO2) and electrolytes (Na+, K+ and Ca++) were measured. MAP was normal in G1-N; severe hypotension, negative inotropic and short MST were observed in G2-SC; normalization of MAP, with lesser negative inotropism and increased MST were observed in G3-SG; full recovery was observed in G4-SE. Histamine level was significantly higher in G2-SC; reduced in G3-SG and G4-SE. PGE2 increased in G3-SG; PGF2 increased in G2-SC and G3-SG. Na+ and Ca++ concentration decreased in sensitized rats but reversed in treated groups, without change in K+ concentration. In conclusion, our data suggest that administration of GLY reduces hypotension and increases survival time in rat anaphylactic shock.