Clearance of rabbit plasma angiotensinogen and relationship to CSF angiotensinogen

Rabbit plasma angiotensinogen was purified 1,390-fold by classical purification procedures. Analytical polyacrylamide gel electrophoresis and direct activity assay revealed that the purified preparations were greater than 90% native angiotensinogen. The purified angiotensinogen was radiolabeled with 125I-Na using the immobilized lactoperoxidase-Sepharose method and injected into awake, conscious rabbits. Complex clearance kinetics were observed that were resolved by a three-component model; half of the protein was cleared rapidly (t1/2 = 6 and 54 min), presumably reflecting mixing and redistribution, whereas half exhibited slow clearance kinetics (t1/2 = 8.58 h). The clearance kinetics were independent of the method of iodination and the isoelectric-point microheterogeneity of the protein. With knowledge of clearance kinetics we tested whether cerebrospinal fluid angiotensinogen could derive from the plasma pool. After injection of approximately 100 microCi 125I-angiotensinogen into the rabbit circulation, little 125I-angiotensinogen was detected in cerebrospinal fluid. Further, the brain space of 125I-angiotensinogen was identical to that of 125I-albumin, a protein that does not partition from plasma into the central nervous system. We conclude that the brain prohormone does not appear to be derived from the plasma pool.