1. Inactive renin in human plasma can be activated by pH 3.3-dialysis (generation of acid-activated renin), by clotting factor XII-mediated prekallikrein to kallikrein conversion after pH has been restored to neutral (generation of acid-kallikrein-activated renin) or by the addition of trypsin (generation of trypsin-activated renin).
2. Natural active renin, acid-kallikrein-activated renin and trypsin-activated renin behave similarly during affinity chromatography on Blue-Sepharose CL-6B and during gel filtration on Sephadex G-100. They also show similar reaction kinetics with similar pH-optimum curves when acting on sheep renin substrate.
3. Acid-activated renin is different. It is retained on Blue-Sepharose columns and it is inactivated at neutral pH during incubation at 37°C. This contrasts with the other forms of renin activated in vitro and with natural active renin. The pH-optimum curve of acid-activated renin, when acting on sheep renin substrate, is also different from that of the other forms of active renin.
4. It is to be proven that the renins generated in vitro by neutral serine proteinases are identical with natural active renin, but clearly they bear more resemblance to natural renin than acid- activated renin does. Our preliminary conclusion is that acid-activated renin is a ‘laboratory renin’, which does not circulate in normal peripheral venous plasma.