Evidence for a role of plasma kallikrein in the activation of prorenin.

Abstract

The proteolytic enzyme renin seems to play an important part in the humoral control of blood pressure by initiating a reaction which finally leads to the production of the vasoconstrictor peptide angiotensin II. However, it has recently been shown that normal human plasma contains a higher molecular weight form of renin (prorenin), which is enzymatically inactive1–6. In vitro, prorenin is converted to the active renin enzyme by various unphysiological procedures such as cryoactivation7–9, acid activation1,6,7,9 or the addition of trypsin10,11 or pepsin11,12, the activation by trypsin being equal to that by acidification13–15. Although the physiological role of prorenin remains unclear, it has been shown that differences exist in the response to stimuli between prorenin and the active renin enzyme3,6,7. Recently, it has been shown that serine protease(s) may be involved in the activation process of prorenin, during both cryoactivation7,16 and acid activation7. Furthermore, human urinary kallikrein added to plasma in low concentrations is able to activate prorenin completely in vitro17. Therefore, it has been speculated that urinary kallikrein might be the physiological in vivo activator of prorenin17–19. This also seemed plausible because renal kallikrein is produced in cells adjacent to the renin-producing cells20. On the other hand, plasma kallikrein has been implicated in the activation of prorenin 15,21–23. In the experiments described below we tried to obtain some more direct evidence for the in vivo role of kallikrein(s) in the prorenin activation. Our results suggest that plasma kallikrein may indeed be a physiological activator of prorenin, but they do not support a role for urinary (renal) kallikrein in the activation of prorenin.