抄録
In order to examine whether substrate specificity of angiotensin-converting enzyme (ACE) exists or not for N-terminal substituted angiotensin I (ANG I) in man, biological activities of sarcosine1-angiotensin I (Sar1-ANG I) and the effects of an ACE inhibitor, captopril, on the Sar1-ANG I activities were studied in 5 normal men. The following 3 experiments were done at 1 week intervals.(1) Sarcosine1-angiotensin II (Sar1-ANG II) was infused iv at a rate of 5 pmol/kg·min from 0900 h to 0930 h in 5 normal men in a recumbent position. Blood pressure rose remarkably and the average increment was 38/31 mmHg at 30 min (p<0.001). Average duration of the pressor action after the cessation of the infusion (T) was 40 min for systolic and 50 min for diastolic and much longer than T of isoleucine5-angiotensin II. Plasma renin activity (PRA) decreased (p<0.01) and plasma aldosterone (PA) increased significantly (p<0.01).(2): Sar1-ANG I was infused iv at a rate of 5 pmol/kg·min from 0900 h to 0930 h. Blood pressure rose to the same extent as in (1)(p<0.001). T was 40 min for both systolic and diastolic and much longer than T of ANG I in man. PRA decreased (p<0.01) and PA increased (p<0.01) significantly.(3): Oral 100 mg captopril was given at 0800 h and Sar1-ANG I was infused iv at a rate of 5 pmol/kg·min from 0900 h to 0930 h. Blood pressure showed no significant change. Sixty minutes after captopril PRA increased markedly (p<0.001) and PA decreased (p<0.001). At 30 min of Sar1-ANG I infusion PRA decreased to the pre-captopril level (p<0.001) and PA was kept at the preinfusion level. From these results it is concluded that the conversion of Sar1-ANG I to Sar1-ANG II is almost complete in normal men and even if N-terminal aspartic acid of ANG I is substituted by sarcosine, substrate specificity of ACE is not demonstrated in man. Sar1-ANG I may possibly inhibit renin release in normal men.
