Incorporation of labeled renin into the tissues of the rabbit.

Our previous work has shown that pure hog renin, when injected into one-kidney, one-clip hypertensive rabbits elicits not only antirenin antibodies but also antibodies to what appears to be an altered form of renin (antigen M). Antiantigen M stains the cytoplasm of smooth muscle cells and certain other cells in tissues of normal and hypertensive rabbits. We now report studies in which pure 125I hog and rabbit renin have been infused into hypertensive rabbits for seven-day periods and the tissues subsequently examined for nondegraded radioactive components. The concentration and the distribution of radioactivity found in different tissues of six rabbits that received hog renin and six that received rabbit renin showed enormous variation, for which there is no reasonable explanation. A very significant amount of radioactivity was found to be incorporated into a high molecular weight or insoluble form that may be antigen M. A major portion of the radioactivity has a molecular weight of about 40,000 and has been assumed to be unaltered 125I renin. In plasma there was a very high molecular weight radioactive component that was capable of binding to antirenin or antiantigen M antibodies to a limited degree. In addition there was a major component with a molecular weight of 68,000 that is not formed in vitro but is produced in vivo. It resembles prorenin in human plasma in that it does not adsorb on pepstatin-Sepharose and does adsorb on Cibacron Blue. However, it differs from prorenin in that it does not bind to antirenin antibodies nor can it be activated by trypsin.