| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
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.
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