Shiro Fujimoto

Peptide Inhibitors of the Renin–Angiotensin System

RENIN is said to split a leucyl–leucine bond in alpha 2 globulin substrate—angiotensinogen—to yield a decapeptide, angiotensin I. Angiotensin I is subsequently converted into an octapeptide, angiotensin II, by a converting enzyme contained in plasma. Angiotensin II has a pressor activity. We have studied the effects of synthetic peptides with a leucyl–leucine bond and their derivatives on the activity of renin in the formation of angiotensin. The peptides were di-, tri-, tetra- and pentapeptides with leucyl–leucine bonds at the C-terminal end, in the middle position, at the N-terminal end or with one of the other structures as shown in Table 1.

Purification and properties of endopeptidase from rabbit red cells and its process of degradation of angiotensin

Abstract Endopeptidase, showing angiotensinase activity in rabbit red cells, was purified by fractionation with (NH4)2SO4, DEAE-cellulose column chromatography and Sephadex G-200 gel filtration. The specific activity of angiotensinase on the purified preparation was increased about 8000-fold compared with that of the crude hemolysate. The peptide bonds cleaved by the enzyme preparation in [α- l -Asp1, Ile5]-angiotensin II were Arg-Val, Tyr-Ile and Ile-His. It was demonstrated that hydrolysis of the Tyr-Ile bond with the enzyme was the first step in the inactivation process of angiotensin. The results indicated that the purified so-called angiotensinase might be an endopeptidase without hydrolytic activity on casein, p- toluenesulfonyl - l - arginine methyl ester and acetyl- l -tyrosine ethyl ester.

Pharmakologische Untersuchungen bei Thiaminmangel I. Änderungen des Katecholamingehalts im Gewebe

(1) The increased tissue catecholamine level of the thiamine deficient rat was shown in the atrium, the ventricle, the brain cortex and in the spleen but not in the brain stem and the adrenal gland. (2) The increased response to tyramine of the thiamine deficient heart is most probably due to the high catecholamine level caused by thiamine deficiency. (3) The increased catecholamine content in the thiamine deficient rat does not result from the increased pyruvic acid.

Potentiation by taurine of the inotropic effect of ouabain and the content of intracellular Ca++ and taurine in the heart

Under certain conditions, taurine (3.0 mM) potentiated cardiac contractile response to ouabain in the normal medium. The potentiation by taurine was also observed in the low K+ medium, in which the positive inotropic effect of ouabain increased. The potentiation as seen in both media was, at least in part, due to the increase by taurine of Ca++ content in the heart. Taurine in the heart was not directly related to this potentiation.

Angiotensinase in red cells.

Abstract Comparison of angiotensinase activity in red cells and plasma from rabbits and the fractionation of the enzyme were studied. 1. (1) Angiotensinase activity in red cells from humans and rabbits was much higher than that in plasma. Angiotensinase activity in red cells and plasma, when horizontal starch block electrophoresis was employed, was the highest in the albumin position under the conditions employed. In red cells, two additional fractions showing angiotensinase activity were demonstrated in the position toward the anodal side further than the albumin position. 2. (2) In order to isolate the enzyme in the albumin position in red cells from rabbit, fractionation with ammonium sulfate and DEAE Sephadex A-50 column chromatography were made. Specific activity of angiotensinase in the purified preparation was increased about 300-fold or more compared with that of the crude hemolysate. It was shown that the activity of angiotensinase was not due to leucine aminopeptidase.

Antihypertensive effect of purified enzyme showing angiotensinase activity from rabbit red cells in rats

In der akuten Phase der Goldblatt-Hypertonie der Ratte verhinderte die Injektion von reiner Angiotensinase ein Aussteigen des Blutdruckes. Die Behandlung war unwirksam bei chronischem Hochdruck.

Plasma angiotensinase activity in liver disease

Abstract The electrophoretic detection of the appearance of plasma angiotensinase activity in the γ-globulin zone, named angiotensinase G, in patients with liver damage was studied using rabbits. Angiotensinase G could not be detected either in liver extract from normal rabbits or from rabbits with experimental liver damage. When normal rabbit plasma was incubated together with liver extract, angiotensinase G activity was demonstrated electrophoretically in the incubation mixture. In vitro experiments indicated that γ- or β- globulin fractions of plasma and a heat unstable substance in microsome fractions of liver cells were essential for the formation of angiotensinase G.