Regulation of plasminogen activation in isolated perfused rat kidney

To better understand the mechanism and regulation of plasminogen activation within the kidney, the release and excretion of plasminogen activator activities was studied in the isolated perfused rat kidney in the absence and presence of plasminogen substrate. In the absence of plasminogen, the kidneys released a constant amount of plasminogen activator activity into both the urine and the perfusate. On continuous infusion of purified human plasminogen into the perfusate, the release of plasminogen activator activity into the urine slightly increased, and plasmin generated could be detected in both urine and perfusate. With the use of specific antibodies against the tissue-type (t-PA) and the urokinase-type plasminogen activator (u-PA), respectively, the activity in the perfusate could be identified as t-PA, whereas the activity in the urine could be ascribed to u-PA. A bolus injection of either antibody into the plasminogen-supplemented perfusion medium completely inhibited plasminogen activator activity and generation of plasmin in the vascular or tubular compartment. Furthermore, intrarenal inhibition of t-PA activity by the specific antibody significantly increased the concentration of plasminogen in the perfusate, indicating decreased consumption. This effect was accompanied by increased excretion of u-PA into the urine, suggesting that the availability of intact plasminogen in the renal circulation directly or indirectly might participate in the regulation of u-PA excretion into the urine.