Evidence for the involvement of a plasma kallikrein-kinin system in the immediate hypotension produced by endotoxin in anaesthetized rats

1 In vitro incubation of normal rat plasma with endotoxin from E. coli (3–10 mg ml−1 in the incubation mixture) caused a dose-dependent increase in levels of free kinin and plasma kallikrein in the presence of o-phenanthroline, together with a mirror-image, dose-dependent decrease in the residual levels of the precursors, plasma prekallikrein and high-molecular-weight kininogen. Low-molecular-weight kininogen levels were not modified. 2 Intravenous injection of endotoxin (3–30 mg kg−1) into the femoral vein of anaesthetized rats resulted in dose-dependent hypotension. In blood collected up to 15 min after injection, the levels of prekallikrein and high-molecular-weight kininogen in plasma were decreased while levels of the active forms, plasma kallikrein and free kinin, showed a transient increase in the blood 1 min after administration of endotoxin. 3 A degradation product of bradykinin, des-Phe8-Arg9-bradykinin, as measured by a newly developed enzyme immunoassay, was detectable up to 5 min after administration of endotoxin. 4 Intravenous infusion of soybean trypsin inhibitor inhibited both the formation of bradykinin and des-Phe8-Arg9-bradykinin and the initial hypotension. 5 It can be concluded from our results that plasma prekallikrein is activated in the blood immediately after administration of endotoxin to rats and that bradykinin is a major cause of the immediate hypotension.