Renomedullary Vasodepressor Substance, Medullin

Abstract

The chemical and physiological properties of renomedullary depressor substances were investigated utilizing the normotensive, vagotomized, pentolinium-treated rat for assay. By a combination of solvent extraction, column chromatography, and thin-layer chromatography, three biologically active acidic lipids were isolated from rabbit renal medulla. The first compound, called medullin, is an acidic lipid with potent vasodepressor and relatively weak nonvascular smooth muscle-stimulating properties. Ultraviolet analysis revealed spectra closely resembling that of prostaglandin E-1 (PGE-1). Infrared analysis showed the presence of carbonyl, methylene, and hydroxyl groups in addition to trans ethylene bonds. Although closely resembling PGE-1, medullin appears to be a more unsaturated carboxylic lipid with less polar (hydroxyl) groups. The hypotensive action of medullin is attributable to a direct effect on peripheral arteriolar beds without cardiac depression, because intra-arterial and intravenous injections of medullin reduced peripheral resistance markedly and increased cardiac output simultaneously. In addition, no effect on cardiac rate or contractility was observed in the isolated rabbit heart preparation. Comparative studies of medullin and PGE-1 indicated that the hypotensive activity of these compounds is similar with respect to potency and mechanism of action. The only biological difference between crystalline PGE-1 and medullin was a fiftyfold greater stimulation of nonvascular smooth muscle by PGE-1 in comparison to medullin. A second biologically active acidic lipid isolated from rabbit medulla was tentatively identified as PGE-1, and was found to possess both vasodepressor and nonvascular smooth muscle-stimulating properties. The third isolate from rabbit medulla possessed potent intestinal stimulating activity but weak to absent vasodepressor effects, properties similar to those of prostaglandin F compounds.