Bradykinin metabolism in perfused rat kidney

The purpose of this study was to assess the capacity of perfused rat kidney to inactivate bradykinin (BK), and to compare the BK degrading capacity of rat kidney with the BK degrading capacities of rat lung, liver, and skelet al muscle, which was approximated by perfusion of rat hind limbs. Radioacti vely labeled BK, with the Pro(2) and Pro(3) residues having been tritiated, in an asanguinous salt solution was perfused through the kidney of the rat , over a concentration range of .0028-33 mu M. Rat kidney had a large capac ity to degrade BK and the system did not appear to approach saturation unti l perfusate BK concentrations reached 24 mu M. A least-squares linear regre ssion analysis and extrapolation to zero concentration was used to obtain v alues for amounts of BK degraded and BK fragments formed. The amount of BK cleaved was 99.9% of the administered dose. The major tritiated BK fragment s formed, and the amount of each expressed as a percentage of the amount of BK degraded during transrenal passage, were the amino acid proline derived from the Pro(2) and/or Pro(3) residues of BK (pro(2,3)), 60%; Pro-Pro (BK 2-3), 12%; Arg-Pro-Pro-Gly-Phe (BK 1-5), 14%; and Arg-Pro-Pro-Gly-Phe-Ser-P ro (BK 1-7), 14%. The formation of BK 2-3 is indicative of initial aminopep tidase-P cleavage of BK to yield Arg, and des-Arg(1)-BK. Thus in rat kidney the aminopeptidase-P pathway is the major route for BK degradation, as is the case in rat liver.