To test whether
endotoxin decreases blood pressure acutely in rats by activating the plasma
kinin-forming system,
plasma kallikrein activity was determined in different experimental settings of
endotoxemia. Conscious normotensive rats were infused for 45 min with
endotoxin (LPS E. coli 0111:B4) at a dose (0.01 mg/min) which had no effect on blood pressure. Additional rats were infused with the vehicle of
endotoxin. Plasma
prekallikrein activity was measured at the end of the 45 min infusions. In other rats, a bolus
intravenous injection of
endotoxin (2 mg) was administered following the 45 min infusion of
endotoxin or its vehicle. In these two latter groups of rats, plasma
prekallikrein activity was determined 15 min after administration of the bolus dose of
endotoxin. In rats pretreated with the
endotoxin infusion, the bolus dose of
endotoxin had no significant effect on blood pressure, whereas rats infused with the vehicle became and remained hypotensive up to the end of the experiment. There was however no significant difference in plasma
prekallikrein activity within the different groups of rats. In another group of rats,
dextran sulfate (0.25 mg i.v.), which activates
factor XII and thereby the conversion of
prekallikrein to
kallikrein, induced a short-lasting fall in blood pressure. 15 min after administration of
dextran sulfate, plasma
prekallikrein activity was almost completely suppressed. These results obtained in unanesthetized rats strongly suggest that the blood pressure fall induced by E. coli
endotoxin is not due to activation of
prekallikrein and consequently of the
kinin-forming system.