Kono T, Taniguchi A, Imura H, Oseko F, Khosla M C
Life Sci. 1986 Apr 21;38(16):1515-9. doi: 10.1016/0024-3205(86)90565-5.
Biological activities of angiotensin II-(1-6)-hexapeptide [ANG-(1-6)] and angiotensin II-(1-7)-heptapeptide [ANG-(1-7)] were studied in 5 normal men and 3 patients with Bartter's syndrome. The angiotensins were infused iv in each subject from 0900 h to 0915 h at a rate of 21 nmol(16.8 micrograms)/kg X min and 18 nmol(16.2 micrograms)/kg X min for ANG-(1-6) and ANG-(1-7), respectively. In the normal men a significant rise in blood pressure was observed by the infusions of both peptides. Average increments of blood pressure for ANG-(1-6) were 17/14, 23/18, 22/15 and 17/14 mmHg at 2, 5, 10 and 15 min, respectively, and those for ANG-(1-7) were 19/15, 20/17, 13/13 and 15/13 mmHg at 2, 5, 10 and 15 min, respectively. The duration of pressor actions after the cessation of the infusions (T) was 10 min for ANG-(1-6) and 20 (for systolic) and 30 (for diastolic) min for ANG-(1-7). T for ANG-(1-6) was shorter than and T for ANG-(1-7) was similar to T for Ile5-angiotensin II (Ile5-ANG II) reported previously in 7 normal men 5 of whom were the same as examined in the present study. On the other hand, both peptides did not cause a rise in blood pressure in the 3 patients with Bartter's syndrome. Both angiotensins did not cause an increase in plasma aldosterone but did cause a significant decrease in plasma renin activity both in the normal men and in the patients. From these results and our previous observations of inactivity of angiotensin II-(5-8)-tetrapeptide, a pressor action of angiotensin II-(4-8)-pentapeptide, and pressor, renin-suppressing and steroidogenic actions of angiotensin II-(3-8)-hexapeptide in normal men, it is thought that ANG-(1-6) and ANG-(1-7) are bound to angiotensin II (ANG II) receptor in the peripheral arterioles and show pressor actions (less than 0.024% and less than 0.028% of Ile5-ANG II, respectively) and suppress renin mainly via short loop feedback and that the shortest biologically active ANG II molecules for pressor, renin-suppressing and steroidogenic actions are Tyr-Ile-His, Val-Tyr-Ile-His and Val-Tyr-Ile-His-Pro-Phe, respectively, in man. It is also evident that ANG-(1-6) is more rapidly metabolized than ANG-(1-7) or Ile5-ANG II in man.
在5名正常男性和3名巴特综合征患者中研究了血管紧张素II -(1 - 6)六肽[ANG -(1 - 6)]和血管紧张素II -(1 - 7)七肽[ANG -(1 - 7)]的生物活性。分别以21 nmol(16.8微克)/千克×分钟和18 nmol(16.2微克)/千克×分钟的速率在0900时至0915时对每位受试者静脉输注血管紧张素,其中ANG -(1 - 6)和ANG -(1 - 7)的输注速率分别为上述值。在正常男性中,输注这两种肽均观察到血压显著升高。ANG -(1 - 6)在2、5、10和15分钟时血压平均升高分别为17/14、23/18、22/15和17/14 mmHg,ANG -(1 - 7)在相应时间的血压平均升高分别为19/15、20/17、13/13和15/13 mmHg。输注停止后升压作用的持续时间(T),ANG -(1 - 6)为10分钟,ANG -(1 - 7)的收缩压持续时间为20分钟,舒张压持续时间为30分钟。ANG -(1 - 6)的T短于先前在7名正常男性中报道的Ile5 - 血管紧张素II(Ile5 - ANG II)的T,其中5名与本研究中的受试者相同;而ANG -(1 - 7)的T与Ile5 - ANG II的T相似。另一方面,这两种肽在3名巴特综合征患者中均未引起血压升高。两种血管紧张素在正常男性和患者中均未引起血浆醛固酮增加,但均导致血浆肾素活性显著降低。根据这些结果以及我们先前观察到的血管紧张素II -(5 - 8)四肽无活性、血管紧张素II -(4 - 8)五肽有升压作用以及血管紧张素II -(3 - 8)六肽在正常男性中有升压、抑制肾素和刺激类固醇生成作用,认为ANG -(1 - 6)和ANG -(1 - 7)与外周小动脉中的血管紧张素II(ANG II)受体结合并显示升压作用(分别小于Ile5 - ANG II的0.024%和0.028%),并且主要通过短反馈回路抑制肾素,在人类中,具有升压、抑制肾素和刺激类固醇生成作用的最短生物活性ANG II分子分别为Tyr - Ile - His、Val - Tyr - Ile - His和Val - Tyr - Ile - His - Pro - Phe。还明显可见,在人类中ANG -(1 - 6)比ANG -(1 - 7)或Ile5 - ANG II代谢更快。