DISTRIBUTION OF A RENIN-RELEASING FACTOR IN THE CENTRAL-NERVOUS-SYSTEM OF THE RAT

We have previously shown that the serotonergic regulation of renin secretion from the kidneys is mediated by a renin-releasing factor (RRF) that is present in both plasma and hypothalamus. The present studies were designed to determine the distribution of RRF in the brain and peripheral tissues and to test whether RRF release could be stimulated in vitro from hypothalamo-hypophyseal explants. RRF levels were determined in vitro by measuring renin release from kidney cortical slices. Addition of hypothalamic extract to rat kidney slices produced a dose-dependent increase in renin release. RRF was measurable in most brain areas with the highest renin-releasing activity in the hypothalamus, cerebral cortex. medulla oblongata and cerebellum. To determine which brain regions contain RRF cell bodies, rats received an intracerebroventricular injection of colchicine to inhibit axonal transport and concentrate RRF in the perikarya. After colchicine treatment, RRF activity in the cerebral cortex, medulla oblongata and cerebellum decreased. In contrast, the hypothalamus had increased RRF activity suggesting that RRF cell bodies are localized in the hypothalamus. Superfusion of hypothalamo-hyophyseal explants with a high potassium Krebs-Ringer solution stimulated RRF release, suggesting that depolarization of hypothalamic neurons can stimulate RRF secretion. Nephrectomy produced a significant increase in RRF concentration in the hypothalamus, suggesting that RRF neurons respond to decreased renin activity or other kidney-related substances in the circulation. The determination of RRF in peripheral tissue revealed minimal renin-releasing activity in the liver, spleen and skeletal muscle extracts. High performance chromatography of hypothalamic extract on a GPC-100 column revealed RRF activity in fractions that were estimated to have a molecular weight of 5,000. These studies suggest that RRF-containing cell bodies in the hypothalamus respond to depolarization by releasing RRF into the circulation. In addition, the hypothalamic content of RRF is regulated by the kidney. Altogether, these data suggest that RRF neurons are part of a neuroendocrine system that regulates renin secretion from the kidneys.