Dextran-induced lowering of prekallikrein proactivator and prekallikrein in rat plasma

The intravenous injection into rats of dextran (average MW 70,000) 10 mg/100 g caused 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 epsilon-aminocaproic acid intraperitoneally (200-300 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 degrees using the method developed by Laake & Vennerød (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.