The Initial Phase of the Dextran-induced Anaphylactoid Reaction in the Rat: A Comparison of Inhibitors of the Blood Pressure Fall

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Abstract
The histamine H2-receptor antagonist cimetidine (25-100 mg/kg) caused a partial inhibition of the pronounced blood pressure fall induced by dextran (Macrodex, 40-100 mg/kg) in the rat. The inhibition by cimetidine could not be distinguished from the inhibition achieved by the serotonin D-receptor antagonist bromolysergic acid diethylamide (BOL, 1-4 mg/kg). Doses of cimetidine and BOL that gave submaximum inhibitory effects separately, showed approximately additive effects when combined. The combined effect of these drugs never exceeded the maximum effects of the drugs separately, whereas injection of tranexamic acid (AMCHA, 100-300 mg/kg) together with cimetidine or BOL, increased the total inhibition. Dextran injected i.v. into rats reduced the level of plasminogen and plasminogen proactivator in plasma. High doses of AMCHA (200 mg/kg) did not inhibit these effects, but significantly increased the lowering caused by dextran of the capacity of high MW kininogen (HMWK) to function as a cofactor in the activation of factor XII. BOL (1-4 mg/kg, Berstad 1981) and cimetidine (50-100 mg/kg) also reduced the cofactor capacity of HMWK in the doses that were required to provide a manifest inhibition of the dextran-induced blood pressure fall. The early phase of the state of shock induced by dextran in the rat can be counteracted at different sites, correlated with histamine and serotonin receptors, and with an effect antagonized by AMCH. The lowest effective doses of cimetidine and BOL, were rather high, suggesting a less specific mechanism for their effects than inhibition at selective receptor sites.