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.

Biosynthesis of prostaglandins in the renal medulla of rabbit

“…The renal medullas were separated from cortex by scissor dissection [7]. The tissue was minced and homogenized in 4 volumes of 0.1 M potassium phosphate buffer pH 7.4 containing 20 mM EDTA, 1 mM reducedglutathione and 5,6,8,9,11,12,14,15-octatritioarachidonic acid.…”

Influence of Prostaglandins A_1, E₁, E₂, and F_2α on Renal Blood Flow and Plasma Renin Activity

“…The mechanism of hypotensive action of prostaglandins is by direct peripheral arter iolar vasodilation [25], When PGA2 was in jected intravenously into the normotensive dog, the fall in blood pressure was associated with a rise in cardiac output and a significant decrease in total peripheral resistance. The increase in cardiac output was due to a baroreceptor-mediated rise in HR.…”

Effects of Prostaglandin A 1 on the Systemic and Coronary Circulations in the Conscious Dog

“…Studies in laboratory animals (9,13,14,(27)(28)(29) and in man (17,(30)(31)(32)(33) have demonstrated potent effects of prostaglandins on central and peripheral hemodynamics through what is believed to be an action on adenyl cyclase, which is not yet fully characterized. The prostaglandin A and E compounds have been shown in experimental animals to cause a lowering of arterial pressure and an associated tachycardia, whereas the prostaglandin F compounds elevate arterial pressure and have a negligible effect on heart rate.…”