Renin inhibition by synthetic phosphatidyl and phosphorylethanolamines

Renin inhibitory effects of about 30 kinds of newly synthesized Phosphatidyl-E and Phosphoryl-E were studied in vitro and in vivo. Among the synthetic Phosphatidyl-E, PE (SEE ARTICLE) SERies were the most potent and these were stronger than natural Phosphatidyl-E. We also confirmed that the converison from the original Phosphatidyl-E, so called prerenininhibitor, to lyso-form to exhibit renin inhibition as mentioned by Sen et al15,16 and Baggio et al.20 was not essential. But a stronger inhibition to renin was observed in PE-72, one of synthetic Phosphoryl-E analogues. PE-104, Phosphoryl-E without long fatty acid chain, was the most potent inhibitor in this study. PE-72 and PE-104 inhibited the reaction between dog renin and substrate in a competitive way. In dogs and rats, Phosphoryl-E decreased hypertensive responce and increase angiotensin I concentration induced by the exogenous renin. Hypotensive effects of Phosphatidyl-E and Phosphoryl-E were also demonstrated in renal hypertensive rats and not in normotensive rats.