Agonistic Activities of Isoleucine⁸-Angiotensin II in Man

抄録

In order to clarify the importance of C-terminal phenylalanine in angiotensin II (ANG II) molecule, agonistic activities of a C-terminal substituted peptide, isoleucine⁸-angiotensin II (Ile⁸-ANG II), were studied in comparison with those of sarcosine¹-, isoleucine⁸-angiotensin II (Sar¹-, Ile⁸-ANG II) and isoleucine⁵-angiotensin II (Ile⁵-ANG II) in 5 normal men. When infused iv at a rate of 600pmol/kg·min for 30min, Ile⁸-ANG II and Sar¹-, Ile⁸-ANG II raised the blood pressure to the same extent (15/15mmHg on the average), while the average blood pressure increase was 21/21mmHg after an iv infusion of Ile⁵-ANG II at a rate of 5pmol/kg·min for 30min. Duration of the pressor action after the cessation of each infusion was 50-90, 90-120 and 10-25min, respectively. In each case plasma renin activity (PRA) decreased and plasma aldosterone (PA) increased. When infused iv at a rate of 10 pmol/kg·min (maximum non-pressor dose) for 120min, both Ile⁸-ANG II and Sar¹-, Ile⁸- ANG II lowered PRA and increased PA gradually, but 100mg oral captopril given immediately before these infusions caused no significant increase in PRA or no significant decrease in PA but again a decrease in PRA and an increase in PA. These results indicate that Ile⁸-ANG II has a very weak pressor (less than 0.83% of Ile⁵-ANG II and same as Sar¹-, Ile⁸-ANG II) and slight reninsuppressing and steroidogenic actions in man and its metabolic degradation is slower than that of Ile⁵-ANG II and that the substitution of sarcosine for aspartic acid in the N-terminus of Ile⁸-ANG II further slows its metabolism. It is now evident that phenylalanine in 8 position is very important in maintaining sufficient pressor, renin-supressing and steroidogenic actions of ANG II but that this amino acid is not indispensable in maintaining more or less the biological activities of ANG II molecule.