Dextran‐Induced Lowering of Prekallikrein Proactivator and Prekallikrein in Rat Plasma

Abstract

The intravenous injection into rats of dextran (average MW 70,000) 10 mg/100 gcaused marked hypotension after a delay of about 5 minutes. Blood samples collected by cardiac puncture at this time were tested for the amounts of prekallikrein activator (PKA) and kallikrein after acetone-and then kaolin activation of the plasminogen-free plasma. PKA was assayed by measuring the initial rate of release of benzoyl arginine esterase (BAEe) activity in a preparation of partially purified human prekallikrein, and kallikrein was assayed by measuring the BAEe esterase activity. Significant reductions of both parameters were registered, and the amount of high molecular weight kininogen (HMWK) present in the plasma was also reduced. Pretreatment of the rats with E-aminocaproic acid intraperitoneally (20Cb300 mg/100 g) abolished the dextran-caused decreases in the plasma levels of the above mentioned factors, and reduced the fall in blood pressure. The addition of purified human HMWK to the plasma before the acetone activation procedure was started, increased the yield of PKA activity in the final enzyme preparation. When PKA was assayed after kaolin activation of plasma at 0" using the method developed by Laake & Vennererd (1973a & b) for the determination of PKA (activated factor XII) in human plasma, no differences were registered between plasma from rats treated with dextran and plasma obtained from control rats. It is suggested that the low PKA activity of the acetone activated enzyme preparation from plasma of rats treated with dextran was due to the loss of HMWK or a fraction of HMWK.

Dextran‐induced Lowering of Parameters of the Kallikrein‐kinin System in Rat Plasma: Significance of Monoamine‐depleting Agents

“…Serotonin, 5-hydroxy-tryptamine creatinine selection of doses and the interpretation of the sulfate complex, and tyramine, tyramine HCI, Sigma results, blood pressure experiments were also car-Chem, Co., St. Louis, Missouri, U.S.A. The figures given in the present paper for the doses of adrenaline, norried out(Briseid et al 1978a). …”

“…Blood pressure measurements were also carried out in rats pretreated as mentioned above. While dextran 10 mg/100 g caused strong and lasting hypotension in control rats (Briseid et a/. 1978a), no alterations in blood pressure took place in the reserpine-treated animals, and the later development of oedemas of the paws was blocked (Parratt & West 1957).…”

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

“…wt. 70,000) in doses of 25-100 mg/kg induced rapid and marked hypotension, whereas 12.5 mg/kg had no clear effect (Briseid et al 1978). Pretreatment of the rats with inhibitors of fibrinolysis like E-aminocaproic acid (EACA) 2000 mg/kg intraperitoneally (Briseid et al 1978) or tranexamic acid (AMCHA) 200 mg/kg intravenously (Berstad, unpublished results) caused a partial blockade of the fall in blood pressure.…”

“…70,000) in doses of 25-100 mg/kg induced rapid and marked hypotension, whereas 12.5 mg/kg had no clear effect (Briseid et al 1978). Pretreatment of the rats with inhibitors of fibrinolysis like E-aminocaproic acid (EACA) 2000 mg/kg intraperitoneally (Briseid et al 1978) or tranexamic acid (AMCHA) 200 mg/kg intravenously (Berstad, unpublished results) caused a partial blockade of the fall in blood pressure. AMCHA also increased two effects induced by dextran on the high molecular weight kininogen (HMWK) in rat plasma: The lowering of the plasma level of HMWK as measured by the loss of the kinin part of the molecule , and the conversion of HMWK into a substance with low capacity as cofactor for the activation of factor XI1 in the presence of kaolin (Briseid & Berstad 1981;Ber-stad, unpublished results).…”

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

“…RIoodpres.rure e.uperiment.s. T h e intravenous injection of H M r dextran in doses of 40-100 mg/kg induced a rapid and lasting hypotension in the Sprague-Dawley rats used, as previously registered in Wistar rats (Briseid et a/. 1978;Berstad 1982).…”