Activation and reinactivation of inactive renin in normal human plasma

Various facets of activation of inactive renin by acidification or cold exposure were investigated in normal human plasma. The acid activation obtained by titration was usually less than that by dialysis method, but varied from 41% to 122% of the latter. The acid phase of acid activation accounted for about 70% of the total activation achieved by the combined effects of the acid and alkaline phases on the average, and was not affected by any of the inhibitors for serine, thiol or carboxyl protease, whereas serine protease inhibitors suppressed the activation of both renin and plasma kallikrein in the alkaline phase of acid activation. A different mode of plasma kallikrein activation suggested some difference in the mechanism between the alkaline phase of acid activation and the cryoactivation. A part of cryoactivation of renin was independent of the action of plasma kallikrein. The renin activated by either acidification or cold exposure without concomitant activation of plasma kallikrein was reinactivated by the removal of pH and temperature, but recovered by repeating acidification or cold exposure. When active plasma kallikrein had been produced, it activated inactive renin irreversibly. It appears unlikely that irreversible activation of inactive renin is taking place in the normal circulation where practically no active plasma kallikrein is present.