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.
Katori
M
M
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Majima
M
M
Odoi-Adome
R
R
Sunahara
N
N
Uchida
Y
Y
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D004731:Endotoxins / Q000008:administration & dosage; D007022:Hypotension / Q000139:chemically induced / Q000503:physiopathology*; D007124:Immunoenzyme Techniques; D007610:Kallikreins / Q000502:physiology*; D007705:Kinins / Q000502:physiology*; D008297:Male; D011288:Prekallikrein / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000503:physiopathology*; D014361:Trypsin Inhibitors / Q000494:pharmacology
D004731:Endotoxins; D007705:Kinins; D014361:Trypsin Inhibitors; C050809:bradykinin, des-Phe(8)-des-Arg(9)-; D011288:Prekallikrein; D007610:Kallikreins; D001920:Bradykinin