A Non-dialysable, Heat-stabile, Hypertensive Substance in the Serum of Rats

Abstract

INCUBATION of rat serum at 37° C, without any digestion by proteolytic enzymes or change of the pH, effects the liberation of a highly pressure-active substance. This hypertensive effect appears after an incubation of 5 h and reaches its maximum after 15 h at 37° C (Fig. 1A). The blood pressure of rats nephrectomized 24–48 h before or after application of a ganglionic blocking agent or infusion of hypotonic glucose is controlled. 0.25 ml. of incubated serum given intravenously causes a rise of the blood pressure of about 35 mm mercury; this equals, in terms of pressor activity, 0.05 (µg of ‘Hypertensin’ (CIBA). Infusion of a hypertonic sodium solution diminishes the hypertensive effect both of the incubated serum and of synthetic angiotensin (hypertensin (CIBA)). Incubation of serum during a period longer than 40 h slowly reduces the hypertensive activity of incubated serum. The hypertensive substance is not dialysable against sodium chloride. Ultrafiltration across a cellulose membrane is not possible (Fig. 1B). The pressure-active principle is found at 40–60 per cent saturation with ammonium sulphate. Boiling of this fraction at pH 1 for 10 min is sustained without any reduction in hypertensive effect; at pH 12 the hypertensive principle is destroyed.