In vitro evidence for a blood-borne renin-releasing factor.

The present studies using kidney slices were designed to test whether serotonergic stimulation of renin secretion is mediated via an endocrine signal. Previous in vivo studies have indicated that central serotonergic neurons regulate renin secretion. Administration of the serotonin releaser dl-p-chloroamphetamine-HCl (PCA) to rats causes dose-dependent increases in renin secretion that can be blocked by serotonin depletion with p-chlorophenylalanine (PCPA), injections of 5,7-dihydroxytryptamine into the dorsal raphe nucleus or ablation of the mediobasal hypothalamus. The renin-releasing substance was obtained from nephrectomized male donor rats which were sacrificed 1 hour after receiving an injection of PCA intraperitoneally. Plasma from rats that received saline injections was used as control. The plasma was collected and separated by ultrafiltration into fractions containing solutes with molecular weights between 500-10,000 daltons. The renin-releasing ability of this substance was studied in vitro using rat renal cortical slices. The plasma fraction (M.W. = 500 - 10,000) from rats treated with PCA caused dose-dependent increases in renin release from the kidney slices. Heating of the plasma factor at 100 degrees C for 30 minutes did not reduce the ability of this substance to release renin from the kidney slices. PCA alone (66 X 10(-6)M) did not increase renin release from the kidney slices. These data suggest that stimulation of serotonergic receptors in the brain triggers the release of an endocrine factor that is capable of directly stimulating renin release from the kidneys.