Partial characterization of a renin-releasing factor from plasma and hypothalamus

Previous studies have indicated that administration of the serotonin releaser p-chloroamphetamine HCl produces a dose-dependent increase in renin secretion through a blood-borne renin-releasing factor. The present studies were designed to partially characterize this renin-releasing factor using an in vitro kidney slice method for the bioassay of renin-releasing activity. Plasma from p-chloroamphetamine-treated, nephrectomized rats was used to obtain the renin-releasing factor, which was fractionated by ultrafiltration into fractions of molecular weight ranges of 1000 to 5000, 5000 to 10,000, and 10,000 to 20,000. The molecular weight ranges of the renin-releasing factor was determined to be between 5000 and 10,000. Since previous studies have shown that lesions in the hypothalamus prevent the effect of p-chloroamphetamine on renin secretion, we tested whether a hypothalamic extract can release renin from kidney slices. Addition of extracts of boiled rat hypothalamic tissue to the kidney slices caused an increase in renin release. Addition of cerebellar extracts produced a smaller increase in renin release, whereas addition of pituitary extracts had no effect. Fractionation by ultrafiltration of bovine hypothalamic extract revealed that the fraction with a molecular weight range of 5000 to 10,000 possessed the highest renin-releasing ability. The 1000 to 5000 (molecular weight) fraction possessed a sizeable renin-releasing activity, but the 10,000 to 20,000 fraction had no renin-releasing activity. Both bovine hypothalamus fractions (molecular weights between 1000-5000 and 5000-10,000) and plasma fraction lost their renin-releasing activity after digestion with pronase, suggesting that the renin-releasing factor or factors are peptides. These results suggest that a renin-releasing factor originate in the hypothalamus.