leukotriene-b4 and Hypotension

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.

Topics: Allergens; Anaphylaxis; Animals; Arterial Pressure; Dinoprost; Dinoprostone; Glyburide; Heart Rate; Histamine; Hypotension; Leukotriene B4; Male; Ovalbumin; Potassium Channel Blockers; Rats; Rats, Wistar

Periodic systemic capillary leak syndrome (Clarkson disease) is characterized by unexplained attacks of a marked increase in capillary permeability. As leukotrienes, derived from arachidonic acid via the 5-lipoxygenase pathway, enhance capillary permeability, we studied arachidonate metabolism in leucocytes of a patient with capillary leak syndrome. Leucocyte-platelet suspensions, prepared from blood collected from the patient during asymptomatic periods (n = 11) produced greater amounts of 5-hydroxyeicosatetraenoic acid (5-HETE) than control suspensions (P less than 0.05). Peripheral leucocytes, collected during attacks (n = 3) and studied without addition of A23187 released LTB4 in vitro but not sulphidopeptides leukotrienes. This result was never observed with leucocytes from control subjects or from the patient out of a crisis. These results suggest that in the patient, peripheral leucocytes could be stimulated by an unknown, as yet to be determined, endogenous factor to produce more 5-HETE and LTB4. Whether LTB4 plays a pathogenic role in the capillary leakage remains to be determined.

Topics: Adult; Arachidonate 5-Lipoxygenase; Arachidonate Lipoxygenases; Calcimycin; Capillary Permeability; Chromatography, High Pressure Liquid; Female; Humans; Hydroxyeicosatetraenoic Acids; Hypotension; Leukocytes; Leukotriene B4; Male; Radioimmunoassay; SRS-A