| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
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.
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