Renin Inhibition by Synthetic Phosphatidyl and Phosphorylethanolamines

• Published in: JAPANESE CIRCULATION JOURNAL Vol. 40; no. 8; pp. 901 - 910
• Main Authors: MIYAZAKI, MIZUO, KANOO, HOSOKI, YAMAMOTO, KENJIRO
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Circulation Society 01.01.1976
• Subjects: Angiotensinogen; Animals; Blood Pressure - drug effects; Chemical Phenomena; Chemistry; Dogs; Ethanolamines - pharmacology; Organophosphorus Compounds - pharmacology; Phosphatidylethanolamine; Phosphorylethanolamine; Rats; Renin - antagonists & inhibitors; Renin inhibitor
• ISSN: 0047-1828; 1347-4839
• DOI: 10.1253/jcj.40.901

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 (β-C=318, γ-C18) series were the most potent and these were stronger than natural Phosphatidyl-E. We also confirmed that the conversion from the original Phosphatidyl-E, so called prerenininhibitor, to lyso-form to exhibit renin inhibition as mentioned by Sen et al. and Baggio et al. 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 increased 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.