Significant reductions were registered in the plasma levels of prekallikrein proactivator (pro‐PKA), prekallikrein (PK), and high molecular weight kininogen (HMWK) 3‐5 min. after the intravenous injection into rats of serotonin (0.02‐0.20 mg/kg) or noradrenaline (0.02 mg/kg), whereas adrenaline (0.02 mg/kg) showed no effect, and tyramine (3.0 mg/kg) only slightly lowered the parameters mentioned. Pretreatment with reserpine (1.5 mg/kg) injected intraperitoneally 24 hours before dextran (10 mg/100 g) inhibited the dextran‐induced lowering of pro‐PKA and PK, but not the lowering of HMWK, while the effects of serotonin (0.13 mg/kg) were not influenced. After pretreatment of the rats with guanethidine (150 mg and 150 mg/kg respectively 48 hours and 24 hours before dextran) the dextran‐induced reductions in the levels of pro‐PKA and PK took place to the same extent as in control rats. while the lowering of HMWK was abolished. Pretreatment with reserpine protected against dextran‐induced oedemas, whereas pretreatment with guanethidine did not. It is concluded that catecholamines are probably not important in the initial phase of the dextran reaction in the rat, whereas serotonin seems to be an essential factor at this stage, as it is known to be during the fully developed dextran reaction. The results indicate that HMWK is not essential in connection with the early events of the dextran reaction, whereas the parameters pro‐PKA and PK seem to be of primary importance during this phase.

No abstract

Incubation of plasminogen-free rat citrated plasma with acetone (23 % v/v) yielded enzyme preparations with high levels of plasminogen activator (PGA) and kininogenase (kallikrein), but with a low concentration of high molecular weight kininogen (HMWK) active as cofactor for kaolin-induced activation of factor XII. When benzamidine (4.0 mM) was present during acetone activation, a high yield of functionally active HMWK was obtained. Gel chromatography separated PGA into one high molecular weight fraction (HMW-PGA) without kininogenase and BAEe esterase activity, and one fraction (LMW-PGA) eluting together with plasma kallikrein. Injection of dextran (100 mg/kg intravenously) reduced the amount of LMW-PGA to 40%. without altering the concentration of HMW-PGA, and with only a small reduction of the kininogenase activity.

The anti‐inflammatory effects of adrenaline, isoprenaline, noradrenaline, tyramine, reserpine, guanethidine and fibrinolysin® were tested against carrageenin‐induced rat paw oedema. All the substances significantly inhibited the oedema. The inhibition by tyramine enhanced the effect of reserpine. The MAO‐inhibitor iproniazid potentiated the effect of noradrenaline and reduced the effect of reserpine. The in vivo effects of adrenaline, noradrenaline, reserpine and fibrinolysin on parameters of the plasma kinin system were investigated. Neither kininogen nor prekallikrein was influenced by any of the substances tested. The effect of noradrenaline, reserpine and guanethidine on the blood serotonin level was also investigated. Noradrenaline and guanethidine did not influence the serotonin level under experimental conditions which cause a significant reduction in the carrageenin‐induced rat paw oedema. The depletion by reserpine of the serotonin stores did not correlate with the rat paw oedema inhibition values. Nevertheless, a slight reduction in the blood concentration of serotonin after pedal injection of carrageenin might indicate a local release of the amine. Finally, plasminogen was estimated by a caseinolytic procedure in the plasma of rats injected with noradrenaline. Noradrenaline inhibited the rat paw oedema, but no reduction of the plasminogen level was observed. It was concluded that normal catecholamine stores rather than normal serotonin stores, and the application to the blood platelet serotonin, seemed essential for the development of carrageenin‐induced rat paw oedema. The fact that pretreatment with catecholamines inhibited the development of oedema might suggest that the same pathway of biochemical events is involved in the inflammatory process and in the preventive mechanism, the inhibition then reflecting an acute activation and depletion of a factor later in the sequence.

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.