INACTIVATION OF ATRIAL NATRIURETIC SUBSTANCE BY KALLIKREIN

To further characterize the properties of the potent natriuretic and diuretic substance that can be extracted from atrial tissue, its susceptibility to inactivation by kallikrein and other proteolytic enzymes was investigated. Extracts of rat atrial tissue (tissue wet wt 100 mg/ml) were incubated with enzymes under standard conditions and tested by injection into nondiuretic anesthetized rats. One h of incubation at 37.degree. C with pure porcine pancreatic kallikrein at concentrations of 250 .mu.g/ml or greater significantly reduced the activity of atrial natriuretic substance. The reduction in activity was dependent on both enzyme concentration and time of incubation. The kallikrein-catalyzed degradation was completely blocked by aprotinin but was only partially retarded by soybean trypsin inhibitor. Trypsin reduced natriuretic and diuretic activity of extracts at concentrations of 400 .mu.g/ml or greater, with nearly complete inactivation at a concentration of 1000 .mu.g/ml. Carboxypeptidase B also caused a concentrated-dependent inactivation of the natriuretic material. Last, .alpha.-chymotrypsin (1000 .mu.g/ml) and elastase (1000 .mu.g/ml) were found to destroy the natriuretic activity. In a separate set of experiments natriuretic activity was observed to be retained by a 1000 MW cutoff membrane. Inactivation of the natriuretic peptide by renal kallikrein is a possible mechanism for in vivo regulation of natriuretic activity.