2005 Fiscal Year Final Research Report Summary
Elucidation of antihypertensive mechanism of small peptides and new proposal of physiological functional foods
| Project/Area Number |
15380094
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Food science
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
MATSUI Toshiro Kyushu University, Faculty of Agriculture, Associate Professor, 大学院・農学研究院, 助教授 (20238942)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMOTO Kiyoshi KYUSHU UNIVERSITY, Professor, 大学院・農学研究院, 教授 (80038322)
KIMOTO Koichi Tokyo Kasei University, Department of Nutritional Science, Professor, 栄養科学科, 教授 (60133378)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Hypertension / renin-angiotensin system / peptide / Ca channel blocker / side-effect / absorption / ACE |
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| Research Abstract |
This study has focused on the elucidation of antihypertensive mechanism of bioactive small peptides on rat and cell-line experiments. Typical and new findings are as follows:
1.Di-peptide, Val-Tyr(VY) with antihypertensive ability in mild hypertensive human showed an age-dependent blood pressure lowering ; a prominent lowering effect was observed in 18-wk SHR after a single oral administration of 10 mg/kg VY, whereas less effect was obtained in 24-wk SHR.
2.As a result of peptide absorption study in 18-wk SHR, intact VY absorption was observed in the circulating blood system as well as local organ systems, in particular in the kidney and abdominal aorta the peptide was predominantly accumulated at ng/g-tissue level. Thus, it was found that VY absorbed preferably into local organs rather than blood system.
3.To clarify whether ACE inhibitoty peptides act as a bradykinin potentiator or not, correlation between peptide structure and C-/N-domain blockade of ACE was investigated. Among 65 synthetic peptides, a significant N-domain ACE inhibition was observed only for Ile-Tyr and Ile-Phe-Tyr. Knowledge on hydrophobic energy of peptides provided a useful information that peptides or compounds having the restrictive energy of 10.8 to 12.5 kJ/mol could inhibit N-domain ACE activity..
4.A potential physiological function of small peptides having ACE inhibitory activity was examined using human vascular smooth muscle cell (VSMC). As a result, VYsignificantly inhibited VSMC growth with a reduction to 59.5 % of control. In addition, inhibition of increase in 1 μM Ang II-stimulated WST-8 incorporation was observed only for VY among tested ACE inhibitory peptides. The VY-induced inhibition was not affected in the presence of AT_1 receptor antagonist (1 μM of losartan) at all. Finally, VY inhibited a Bay K 8644-stimulated VSMC proliferation, indicating that VY with ACE inhibitory activity also acts as an L-type Ca2+ channel blocker.
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