Vasotoxic Activities of Renal Lysosomal Contents: Especially Renin

Abstract

As it was reported already, the Ly-C from the hog renal cortex produced fibrinoid necrosis of the small arteries and arteriols in the bilaterally nephrectomized rats. The vasotoxic substances in the Ly-C were partially purified and both the affinity positive, rich in renin and glycoproteins, and negative fractions for concanavalin A were shown to have vasotoxic activities, the details of the latter were reported previously. The present study was carried out to answer the question whether fibrinoid necrosis produced by the affinity positive fraction of Ly-C was due to the elevated pressure by renin or the direct biochemical effect of renin on blood vessels or some other factors other than renin.
METHODS The Ly-C obtained from the hog renal cortex by differential centrifugation and osmotic shock treatment as reported previously. A further purification of the Ly-C was performed by the concanavalin A-Sepharose 4B column.
In order to determine whether fibrinoid necrosis produced by renin is due to elevated blood pressure or its direct biochemical effect, some of the conscious bilaterally nephrectomized rats were treated with SQ14225 to prevented an elevation of the blood pressure prior to the administration of the samples. Blood pressure of the rats was monitored continuously by the cannulation of carotid artery.
RESULTS Fractionation and Concanavalin A Affinity Column Chromatography of Lysosomal Contents: A contamination of Ly-C by the microsomal and mitochondrial fractions appeared to be approximately 1% in terms of specific activity of marker enzymes. The renin activity was detected mainly in Ly-C. When Ly-C were applied to concanavalin A affinity column, glycoprotein fractions containing renin were absorbed completely by Sepharose 4B-concanavalin A and eluted with methyl-α-D-glucoside.
Blood Pressure and Vascular Lesions: The affinity fraction containing renin (fraction B) as well as no affinity fraction (fraction A) of Ly-C produced similar angionecrosis of a fibrinoid type. When the fraction B was injected into the rats, the mean blood pressure was elevated. The microscopic studies of these rats revealed consistently fibrinoid type angionecrosis in the smaller arteries and arteriols of the pancreas, mesenterium and heart. In order to prevent an elevation of blood pressure by the fraction B SQ14225 was administrated orally one hour before the injection of the fraction B. An elevation of the mean blood pressure was mild and transient and angionecrosis was not produced.