In an effort to explore the possible role of fibrinolytic enzyme system in the pathogenesis of so-called essential renal bleeding, the author has previously reported several findings for this enzyme system in the blood, urine, and renal tissue of rabbits with renal bleeding produced experimentally by Reilly's phenomenon or by the use of serotonin or bradykinin.
The results indicate that hematuria with concomitant alterations in fibrinolytic enzyme system in Reilly's phenomenon occurs at relatively early stage.
The present report represents an attempt to clarify the pattern of changes in enzyme activators and proactivators of the renal tissue (at 1-1/2, 20, and 30min. post irritation respectively) occurring in Reilly's phenomenon, with particular reference to the effect of streptokinase (SK) on it.
1. Plasma assays for fibrinolytic activity on the standard fibrin-plates with and without SK added revealed the plasma samples obtained 1-1/2min. after irritation to be practically comparable in fibrinolytic activity to those obtained prior to irritation, whereas the inhibitor showed a tendency to increase. At 20min. post irritation, there was practically no evidence of the presence of inhibitor or proactivator in the plasma, while a rise in the activator level was evident. Increased proactivator level was observed, however, in the plasma samples collected at 30min. after irritation.
2. In the renal cortex of healthy rabbits, a plurality of proactivators was demonstrably present in abundance, and activation of the proactivators was found to occur in Reilly's phenomenon as examined with the crude renal tissue preparations obtained 15min. following irritation.
In the medulla of normal kidneys, on the other hand, there was evidence of the presence of plurality of enzyme activators in abundance as well as of small amount of proactivators. And, in response to Reilly's phenomenon, the level of activators in the renal medullary tissue became lowered while that of proactivators subject to activation by streptokinase remained unchanged, wherein activation of proactivators was allayed as the amount of streptokinase added was increased.
3. Using saline and potassium thiocyanate extracts of a series of renal tissues obtained at various time intervals from rabbits following Reilly's phenomenon, assays of the tissue for fibrinolytic activity (according to the method described by Astrup for extraction of a “stable” activator) were performed with particular reference to the influence of SK with the following results:
a) Occurring naturally in abundance in the renal cortex of normal rabbits, a “stable” activator (Astrup) decreased markedly 1-1/2min. post irritation, and thereafter increased gradually to restore even a little greater value than the pre-irritation level at 30min, post irritation.
The proactivator in renal cortex was found to be best extractable with physiologic saline (i. e. 0.9% NaCl). The level of this proactivator was profoundly elevated at 1-1/2min. after irritation, and a gradual decrease of the level followed. I observed evidence of the presence of proactivators in the supernatant of potassium thiocyanate (2M) cortical extracts, as well.
b) The activator in renal medulla was reasonably well obtained by Astrup's potassium thiocyanate extraction, whereas with physiologic saline, it turned out in small quantities. The activator in renal medulla has proven to markedly diminish at 1-1/2 min, post irritation (p. i.), to rise conversely a little higher than the normalcy, at 20 min. p. i., and again to decrease at 30min. p. i.
The proactivator in renal medulla, like that of the cortex, was best extractable with physiologic saline. Its level was lowered at 1-1/2min. p. i. and, thereafter, gradually elevated to a value greater than the normalcy at 30min. post irritation. Evidence indicates that it is present in the supernatant of potassium thiocyanate extracts of the renal medulla, and
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