More than half of the circulating renin in man exists as an inactive form. Mounting evidence suggests inactive renin is the biosynthetic precursor of renin, i.e. prorenin. Our hypothesis is that 1) conversion of prorenin to renin participates in the regulation of renin production, 2) this conversion is mediated by limited proteolysis involving specific processing enzymes, and 3) various tissues in the body have different capabilities in accomplishing this conversion. Our specific objectives are to 1) purify expressed human prorenin, 2) use purified prorenin to develop assays for the processing enzyme that converts proenin to renin, 3) study in vivo and in vitro activation of expresses prorenin, and 4) purify the renin processing enzyme from human kidney. The long-term goal will be to determine whether conversion of prorenin to renin is a regulatory step in renin production. Ultimately, we hope to determine whether control or renin processing could be used to correct renin deficiency or excess states in man, such as the syndrome of hyporeninemic hypoaldosteronism or such as high and normal renin essential hypertension. Control of the processing enzyme may prove to be a new means to regulate hormone and enzyme production.