Regulation of human renin-angiotensin system by functional food components and elucidation of depressor mechanism

为了阐明Val-Tyr(VY)的体内降压作用，对其在人体循环血液系统中的吸收行为进行了初步研究。轻度高血压病患者口服VY饮料(0、6、12 mg/100ml)后，2小时血压显著下降(P&lt；0.05)(？SBP/？DBP=13/9 mm Hg)。与这种降压行为相一致的是，血浆中VY水平逐渐升高至2小时(2137 fmol/ml血浆)，然后迅速下降至基线水平。(t_&lt；1/2&gt；3.1小时)。此外，血浆血管紧张素(Ang)I和Ang II水平与VY吸收行为密切相关。用人肾素-血管紧张素(RA)系统对筑波高血压大鼠(THM)进行了进一步研究。单次灌胃VY(0.1 mg/g小鼠)，1h后THM血压下降约20 mm Hg，Ang II显著下降。这一结果强烈提示外源性VY对人体循环RA系统有影响。人血管肌细胞实验还表明，VY既是局部血管紧张素转换酶的抑制因子，又是循环血管紧张素转换酶的抑制因子，加入VY(10μc)可显著抑制血管平滑肌细胞的增殖。因此，这些发现强烈地提示，VY可能作为一种降压肽，对循环和局部(主动脉)RA系统起抑制作用。

In order to elucidate the depressor effect of Val-Tyr (VY) with in vivo antihypertensive effect, absorption behavior into human circulating blood system was primarily investigated. After oral adiminstration of VY drink (0, 6, 12 mg/100ml) for mild hypertensive subjects, a significant (P < 0.05) blood pressure (BP) reduction was observed at 2 h (?SBP/?DBP = 13/9 mmHg). Consistent with this BP reduction behavior, VY level in plasma gradually increased to 2h (2137 fmol/ml-plasma) and then rapidly decreased to the baseline level. (t_<1/2> 3.1h). In addition, angiotensin (Ang) I and Ang II levels in plasma closely correlated with the VY absorption behavior. Further study by using TSUKUBA Hypertensive Rat (THM) with human renin-angiotensin (RA) system was done. As a result of single oral administration of VY (0.1 mg/g mouse), about 20 mmHg BP reduction of THM as well as significant Ang II decrease were observed after 1h of administration. This result strongly suggested that exogenous VY affected the human circulating RA system. Human vascular muscle cell (VSMC) experiment also revealed that VY acted as an inhibitor of localized ACE as well as an inhibitor of circulating ACE, in which multiplication of VSMC cell was markedly suppressed by VY addition (10 μc). Consequently, these findings strongly led to the suggestion that VY may act as a depressor peptide towards the inhibition of circulating and localized (aorta) RA systems.