Functionally active high molecular weight-kininogen was found in the liver, but not in the plasma of brown Norway Katholiek rat.

Plasma and liver levels of high molecular weight (HMW-) kininogen were assessed by a newly developed radioimmunoassay in B/N-Katholiek strain rats, which is congenitally deficient in plasma HMW- and low molecular weight (LMW-) kininogens. The plasma level of immuno-reactive HMW-kiniogen in this strain was about 4% of that of the normal strain, B/N-Kitasato, whereas its level in B/N-Katholiek liver was approximately 60% of that in normal strain liver. There was no significant difference of half-life of HMW-kininogen in the circulating blood between the deficient and normal rats. When secretion of HMW-kiniogen from the liver cells of the two strains was examined by primary culture of their hepatocytes, the hepatocytes from the deficient strain did not secrete HMW-kininogen in the medium. HMW-kininogens were isolated from the liver microsomal fractions of both strains by use of an immuno-affinity column. The isolated protein from B/N-Katholiek liver showed similar mobility on SDS-PAGE to that from normal rat liver, and had biological activities of HMW-kininogen purified from normal rat plasma, such as intrinsic blood clotting cofactor, thiol-proteinase inhibitor, and kinin precursor. These results indicate that the plasma deficiency in the B/N-Katholiek strain is due to a defect of HMW-kininogen secretion from the liver.