Hiwada Kunio

Peptide inhibitors of renin angiotensinogen reaction system

Abstract Methyl or ethyl esters of synthetic tetrapeptides, Leu-Leu-Val-Tyr and Leu-Leu-Val-Phe, acted as competitive inhibitors in the renin renin-substrate reaction system. The chemical structures needed for the anti-renin activity were presumed to be as follows: (1) a Leu-Leu bond at the N -terminal end of the tetrapeptide; (2) a Leu-Leu bond with L -Leu at the N -terminal end; (3) the presence of Tyr or Phe at the C -terminal end; (4) the replacement of Val in position 3 by Leu did not reduce the activity; (5) the amide formation of the carboxylic acid of the C -terminal amino acid reduced the activity, but deoxidation produced little change in the activity; (6) the coupling of benzyloxycarbonyl or sodium metasulfonic acid group to the N -terminal end markedly reduced the activity; and (7) the addition of His to the N -terminal end caused almost no change in activity. The pressor response produced by renin injected intravenously into a rabbit being treated with an infusion of the tetrapeptide solution was inhibited compared with that in the control animals.

Isolation and identification of a renin inhibitor from ox bile

Abstract A renin inhibitor in ox bile was purified by ammonium sulfate fractionation, dialysis and chromatography on Bio-Gel P-2 and Amberiite XAD-2 resin. The inhibitor was shown to be taurodeoxycholic acid by means of nuclear magnetic resonance spectroscopy, gas chromatography, amino acid and elemental analyses. Further confirmation of the assignment was established by the direct comparison of its infrared spectrum with that of an authentic sample. Taurodeoxycholic acid inhibited the reaction of rabbit renin with angiotensinogen in vitro . Glycocholic acid, also present in ox bile, however, had no inhibitory effect on the renin angiotensinogen reaction.