AJP - Renal Physiology, Vol 256, Issue 5 787-F793, Copyright © 1989 by American Physiological Society
Regulation of plasminogen activation in isolated perfused rat kidney
W. Muellbacher, M. Maier and B. R. Binder
Department of Medical Physiology, Medical Faculty, University of Vienna, Austria.
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.
