Glyburide, a K(+)(ATP)channel blocker, improves hypotension and survival in anaphylactic shock induced in Wistar rats sensitized to ovalbumin.
Allergens can induce anaphylactic shock and death due to serve 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 40 mg/kg); G4-SE=Sensitized-EPI (epinephrine 10 mg/kg). G2 to G4 groups were sensitized with ovalbumin (OVA) and shock was induced by i.v. injection of OVA. Treatments were administered intravenously 5 min later. Mean arterial pressure (MAP), heart rate (HR), and mean survival time (MST) were measured for 60 min following OVA injection and treatments administration. At the end of the experiment, blood withdrawal was performed to measure plasma levels of histamine, leukotriene B(4) (LTB(4)), prostaglandin E(2) (PGE(2)) and prostaglandin F(2) (PGF(2)). 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. PGE(2) increased in G3-SG; PGF(2) 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 reduced hypotension and increases survival time in rat anaphylactic shock.
Subramanian
S
Dhanasekaran
Abderrahim
A
Nemmar
Elhadi H
EH
Aburawi
Elsadig E
EE
Kazzam
Abdishakur
A
Abdulle
Moufida
M
Bellou
Abdelouahab
A
Bellou
D000485:Allergens; D000707:Anaphylaxis / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D015237:Dinoprost / Q000097:blood; D015232:Dinoprostone / Q000097:blood; D005905:Glyburide / Q000494:pharmacology / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000097:blood; D007022:Hypotension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007975:Leukotriene B4 / Q000097:blood; D008297:Male; D010047:Ovalbumin; D026902:Potassium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D000485:Allergens; D026902:Potassium Channel Blockers; D007975:Leukotriene B4; D006632:Histamine; D010047:Ovalbumin; D015237:Dinoprost; D015232:Dinoprostone; D005905:Glyburide