Dextran‐Induced Lowering of Plasminogen Proactivator and Functionally Active High Molecular Weight Kininogen in the Rat

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The intravenous injection into rats of dextran with a molecular weight of 1,000 (LMr dextran) in doses 200 mg/kg induced rapid, but transient falls in blood pressure. Pretreatment of the rats with LMr dextran 200 mg/kg caused a partial inhibition of the profound blood pressure fall induced by the injection of clinical dextran with a molecular weight of 70,000 (HMr dextran), 40 mg/kg. In accordance with previous works (Briseid & Berstad 1981; Berstad & Briseid 1982; Berstad 1982) it was found that the intravenous injection of HMr dextran lowered the plasma levels of plasminogen proactivator (pro‐PGA) and functionally active high molecular weight kininogen (HMrK). Also LMr dextran, 200 mg/kg, induced significant reductions in the mentioned parameters, but less extensive than those obtained by HMr dextran, 40 mg/kg, and pretreatment of the rats with LMr dextran inhibited the subsequent effects of HMr dextran. It is suggested that a dextran‐activated plasminogen activator might be an early link in the mechanism underlying the dextran‐induced state of shock in the rat.

Section: Discussionsupporting

confidence: 94%

supporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Inhibition by Low Molecular Weight Dextran of the Blood Pressure Fall and the Lowering of Plasminogen Proactivator Induced by Clinical Dextran in the Rat

Briseid

1983

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

Berstad

1982

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The histamine H2‐receptor antagonist cimetidine (25–100 mg/kg) caused a partial inhibition of the pronounced blood pressure fall induced by dextran (Macrodexå, 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. Previous works showed that dextran injected intravenously into rats reduced the level of plasminogen (PG) and plasminogen proactivator (pro‐PGA) in plasma (Briseid et al. 1979; Berstad 1980a; Berstad & Briseid 1982). 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 molecular weight 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. It is suggested that 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 on the one hand, and with an effect antagonized by AMCHA, on the other. 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.

Separation of Plasma Kallikrein and a Kallikrein‐like Plasminogen Activator Generated by Acetone in Rat Plasma

Johansen

Briseid

1983

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Plasminogen activator (PGA), kininogenase (Kase) and benzoyl arginine ethyl ester (BAEe) activities generated in plasminogen‐free rat plasma by incubation with acetone (23% v/v) at 22° were purified. The activities passed unadsorbed through columns of DEAE‐Sephadex A‐50 (pH 7.8) and arginine methylester‐Sepharose 4B (pH 8.5). Part of the activities (rat plasma kallikrein) was adsorbed onto a soybean trypsin inhibitor (SBTI)‐ Sepharose 4B column at pH 8.5. At pH 7.0 a fraction with higher ratios PGA/BAEe esterase and Kase/BAEe esterase was also adsorbed. Both fractions could be eluted with 5 mM sodium hydroxide. The fraction not adsorbed at pH 8.5, but adsorbed at pH 7.0 was designated low molecular weight plasminogen activator (LMr‐PGA), a plasminogen activator fraction with higher molecular weight, but without esterase activity being also present (Berstad & Briseid 1982). LMr‐PGA was strongly inhibited by tranexamic acid (AMCA) 0.10 mM, whereas the fraction designated rat plasma kallikrein was not. By polyacrylamide gel electrophoresis Mr‐values in the range 120,000 to 130,000 were established for native samples of both rat plasma kallikrein and LMr‐PGA, whereas Mr‐values of 78,000 to 80,000 were established after treatment with SDS.