No abstract

1. Normal human plasma contains a proactivator of inactive renin. The pro-activator is activated at physiological pH in plasma that has been pretreated with acid. This activation in vitro leads to the conversion of inactive renin into the active form with simultaneous generation of kallikrein activity. 2. The endogenous activator of inactive renin has the same pH profile and inhibitor spectrum as plasma kallikrein. 3. Inactive renin can also be activated by exposure of plasma to exogenous trypsin, and in normal plasma the quantities of inactive renin that are activated after acidification and with trypsin are identical. Prekallikrein (Fletcher factor)-deficient plasma, however, has much lower renin activity after acidification than with trypsin. Thus acid activation of inactive renin depends on plasma prekallikrein, whereas the action of trypsin is independent of prekallikrein. 4. Highly purified tissue (pancreatic) kallikrein, in a concentration of less than 2 X 10(-8) mol/l, activates inactive renin that has been isolated from plasma by ion-exchange chromatography. In this respect it is at least 100 times more potent than trypsin. 5. It is therefore possible that plasma and/or tissue (renal) kallikreins are also involved in the activation of inactive renin in vivo.

It has been reported that inactive (acid-activable) human renin could be converted into the active form by adding urinary kallikrein to acid-pretreated plasma. Without prior acidification, however, only a small portion of the total amount of inactive renin present in plasma was converted (activated) by kallikrein, probably because native plasma contains protease (kallikrein) inhibitors that are destroyed by acid. We have separated inactive and active renin by DEAE-Sepharose column chromatography of normal human plasma at pH 7.5 and a linearly increasing sodium gradient. Inactive renin isolated in this way could be activated at pH 7.5 by highly purified pancreas and urinary kallikreins. With the semipurified preparation of inactive renin, prior acidification was not required for obtaining virtually complete activation by kallikrein. The kallikreins were effective at concentrations as low as 1 x 10(-8) mol/liter. It is therefore possible that one or more tissue kallikreins act as physiological activators of inactive renin.