Blood Pressure Control by the Angiotensin Metabolites and the application to a Functional Food Design.

为了阐明内源性血管紧张素（Ang）代谢物的抑制作用，我们利用tsukuba高血压大鼠（THM）和正常血压的人血浆研究了Angs的代谢行为，特别是Ang（3-4）。采用2,3 -萘-脱醛荧光柱切换高效液相色谱法测定血浆中Angs的浓度。12周THM中测定Ang（3-4）水平（426 fmol/ml-血浆）比野生型大鼠（207 fmol/ml-血浆）高2倍。但其增幅远低于其他Angs （Ang I: THM， 2247 fmol/ml-血浆；WTR； 530 fmol/ml-血浆；Ang II: THM， 143 fmol/ml-血浆；WTR； 53 fmol/ml-血浆）的增幅。这一结果表明，血压（BP）的升高与Ang的代谢有关（3-4），这与人类受试者的结果一致。即血压随着人血浆中Ang（3-4）代谢水平的降低而升高。此外，我澄清了外源性Ang（3-4）的吸收是在口服剂量为3,6,12 mg/杯后立即观察到的。给药后2小时达到最大吸收，8小时内降至正常水平（t1/2: 3.1小时）。正常血压组6 mg Ang未见血压降低（3-4），轻度高血压组血压降低（9.5 mmHg），差异有统计学意义（p<0.001）。此外，单次口服Ang (3-4) （0.1 mg/g小鼠）可使THM在1小时后降低约20 mmHg BP。因此，这些发现强烈提示内源性Ang（3-4）可能作为抑制循环肾素-血管紧张素系统的抑制肽。

In order to elucidate the depressor effect of endogenous angiotensin (Ang) metabolites, we have investigated the metabolic behavior of Angs, especially Ang (3-4), by using TSUKUBA-Hypertensive Rat (THM) and normotensive human plasma. The concentration of Angs in plasma was determined by our proposed fluorometric column-switching HPLC method with 2, 3-naphthalene-dealdehyde. As a result of the determination of Ang (3-4) in THM (12weeks), the level (426 fmol/ml-plasma) was 2-fold higher than that of wild type rat (207 fmol/ml-plasma). However, the increment was much lower than the increments of other Angs (Ang I : THM, 2247 fmol/ml-plasma ; WTR ; 530 fmol/ml-plasma, ANG II : THM, 143 fmol/ml-plasma ; WTR ; 53 fmol/ml-plasma). This result indicates that the blood pressure (BP) promotion would correlate with the metabolism of Ang (3-4), which is in good agreement of the results obtained in human subjects. Namely, BP increased with the decrease in the metabolic level of Ang (3-4) in human plasma. In addition, I have clarified that the absorption of exogenous Ang (3-4) was observed immediately after oral administration of it with the dose of 3, 6, 12 mg/drink. The maximum absorption was observed after 2hr, and the level decreased to the normal level within 8 hr after the administration (t1/2 : 3.1 hr). No BP reduction was observed in normotensive human subjects with the dosage of 6 mg Ang (3-4), while the BP of mild hypertensive human subjects decreased (9.5 mmHg) siginificantly (p<0.001). In addition, about 20 mmHg BP reduction of THM by single oral administration of Ang (3-4) (0.1 mg/g mouse) was observed after 1 hr. Consequently, these findings strongly led to the suggestion that endogenous Ang (3-4) may act as a depressor peptide towards the inhibition of circulating renin-angiotensin system.