Determinants of kinin release in isolated rat hindquarters

We studied the determinants of kinin release into the venous effluent of rat hindquarters perfused with Krebs bicarbonate buffer. Kinin release in preparations perfused with control media (14.6 +/- 2.5-20.7 +/- 6.7 pg/15 min) was surpassed by that in preparations perfused with media containing kininase inhibitors (243 +/- 53 to 276 +/- 78 pg/15 min). Kinin release increased when purified kininogen (from 242 +/- 43 to 3,365 +/- 725 pg/15 min) or kallikrein (from 270 +/- 49 to 30,649 +/- 8,040 pg/15 min) was added to the perfusate. Conversely, kinin release fell when the kallikrein inhibitor aprotinin (from 272 +/- 58 to 122 +/- 27 pg/15 min) or soybean trypsin inhibitor (from 273 +/- 52 to 195 +/- 25 pg/15 min) was added. Both basal and kininogen-induced kinin release were attenuated in preparations perfused with media containing cycloheximide, a protein synthesis inhibitor, but kallikrein-induced kinin release was not. These data suggest that kinin release from perfused rat hindquarters reflects the activity of both the kinin-degrading and kinin-generating pathways and that the latter is sustained by a kallikrein manufactured de novo and by preexistent kininogen(s).