The enzymatic degradation of various angiotensin II derivatives by serum, plasma or kidney homogenate

Six isomers of angiotensin II, differing from one another only with respect to changes made in the aspartic acid situated at the amino end, were incubated with rat serum, human plasma or rat kidney homogenate. The rate at which the isomers were inactivated was studied by measuring pressor effects in nephrectomized rats. In parallel tests, fragments were demonstrated by means of paper chromatography. Compounds with an α-L-Asp 1 configuration were inactivated much more rapidly in serum or plasma than α-D-, β-L-, β-D- or desamino-angiotensin II. When the substances were incubated with kidney homogenate, however, the differences were less marked. Chromatographic studies revealed that, when the α-L-compounds were incubated, not only peptide fragments occurred as a result of aminopeptidasic degradation, but also small quantities (in free form) of all the amino acids contained in the molecule. The α-D-, β-L-, β-D- and desamino-compounds were found to be protected against aminopeptidasic degradation, whereas endopeptidasic degradation proceeded in the same way as in the case of the α-L-compounds. Here, in addition to free amino acids, the isomeric tetrapeptides Asp-Arg-Val-Tyr were also demonstrable. Whereas in the serum of nephrectomized rats approximately 90 per cent of the total degradation process was due to the activity of aminopeptidases and only 10 per cent to that of endopeptidases, the corresponding activity ratio for the enzymes in rat kidney homogenate or in human plasma was approximately 60 per cent: 40 per cent.