The Reversible Activation of Inactive Renin in Human Plasma: Role of Acid and of Plasma Kallikreing and Plasmin

Inactive renin in normal plasma, Factor XII-deficient plasma and prekallikrein-deficient plasma was fully activated by dialysis to pH 3.0 for 24 hours at 4 degrees C. This activation was reversed after neutralization and incubation of the plasma at 37 degrees C. The reversible activation-inactivation was not affected by the presence of soya bean trypsin inhibitor. If acidified normal plasma was neutralized and stood at 4 degrees C, plasma kallikrein, but not plasmin, was generated. This rendered the initial acid-activation irreversible. Since no kallikrein was generated in the deficient plasmas, the acid-activation was reversible in these plasmas even after neutralization and standing at 4 degrees C. Thus the apparent activation of inactive renin by kallikrein in acidified, neutralized plasma is not a direct action by the serine protease on inactive renin but a two-stage process in which the inactive renin is first fully activated by acid treatment and the reverse reaction is prevented by plasma kallikrein.