Katsuhiro Osajima

Antihypertensive effect of valyl-tyrosine, a short chain peptide derived from sardine muscle hydrolyzate, on mild hypertensive subjects.

The present study was conducted to determine whether Valyl-Tyrosine (VY) has an antihypertensive effect on high-normal blood pressure and mild essential hypertension, as well as spontaneous hypertensive rats (SHR). A randomised double-blind placebo-controlled study was carried out on 29 volunteers. A 100-ml drink containing 3 mg of VY and a 100-ml placebo drink were prepared. The subjects were grouped as VY(16M/1F, 45.5 ± 3.2 years, 146.4 ± 2.3/90.5 ± 1.8 mm Hg) and the placebo (P) (11 M/1F, 48.8 ± 3.0 years, 145.5 ± 2.4/92.3 ± 1.8 mm Hg). At 3 weeks of the control (C) period, a VY- or P-drink was administered twice a day for 4 weeks in the experimental (E) period and during the 4-week recovery period, neither drink was given to either group. Blood pressure (BP) was measured every week in the morning in the sitting position. Blood specimens were taken on the last day of the C and E periods. In the VY-group, reduction in systolic (S) and diastolic (D) BP was 9.7 and 5.3 mm Hg (P < 0.001) at 1 week, and 9.3 and 5.2 mm hg (P < 0.001) at 4 weeks, following the start of the e period, respectively. neither sbp nor dbp changed in the p-group. bp in the vy-group increased gradually by the end of the recovery period. plasma angiotensin (ang) i and vy concentrations significantly increased while ang ii and aldosterone significantly decreased after vy administration in the vy-group. vy appeared to have a significant antihypertensive effect on mild hypertensive subjects via ang i-converting enzyme inhibition, as well as shr, but no adverse effects could be detected at all.

Val-Tyr As A Natural Antihypertensive Dipeptide Can Be Absorbed Into The Human Circulatory Blood System

1. Intact absorption of the bioactive dipeptide Val‐Tyr (VY), with in vivo antihypertensive ability in normotensive human subjects, was investigated.

Antiproliferative action of an angiotensin I-converting enzyme inhibitory peptide, Val-Tyr, via an L-type Ca2+ channel inhibition in cultured vascular smooth muscle cells.

Recent antihypertensive studies have demonstrated that small peptides with angiotensin I-converting enzyme (ACE) inhibitory activity had an ability to lower or to modulate a pressor blood pressure response in mild hypertensive subjects. However, the underlying mechanisms still remain unclear. Based on our previous finding that a small peptide, Val-Tyr (VY), was accumulated in the rat aorta and kidney as well as in the circulating blood system, we here investigated whether antihypertensive small peptides exert an antiproliferative effect on serum- or mitogen-induced human vascular smooth muscle cells (VSMCs). Treatment with some ACE inhibitory small peptides (VY, Ile-Trp [IW], and Ile-Val-Tyr [IVY]) had diverse effects on serum-stimulated VSMC proliferation that were independent of their ACE inhibitory activity, though only VY exerted a potent antiproliferative action. VY also showed a greater inhibition of WST-8 incorporation in response to angiotensin (Ang) II-stimulation than the other two small peptides. The attenuation of Ang II-stimulated WST-8 incorporation by VY was not affected by Ang II receptor antagonists (losartan and saralasin ([Sar1, Ile8]-Ang II)), indicating that the antiproliferative action of VY may not be due to the peptides antagonistic effect against Ang II receptors. Treatment with VY had a significant inhibitory effect on the WST-8 incorporation induced by the stimulation of a voltage-gated L-type Ca2+ channel agonist, Bay K 8644. Even in the presence of a K+ channel blocker (paxillin) the inhibition was apparent, suggesting that VY inhibited the proliferation of VSMCs by serving as a natural L-type Ca2+ channel blocker, but not as a K+ channel agonist.

Sardine peptide with angiotensin I-converting enzyme inhibitory activity improves glucose tolerance in stroke-prone spontaneously hypertensive rats.

An enzymatic hydrolysate of sardine protein (sardine peptide, SP) derived from sardine muscle possesses angiotensin I-converting enzyme (ACE) inhibitory activity. In the present study, we investigated the effect of SP on the blood glucose levels in stroke-prone spontaneously hypertensive rats (SHRSPs). Ten-week-old SHRSPs were assigned to three groups. The control group was given tap water for 4 weeks, while the experimental groups were given water containing SP (1 g/kg/d) or an ACE inhibitor, captopril (8 mg/kg/d). Treatment with SP and captopril decreased ACE activity in the kidney, aorta, and mesentery. There were no differences in fasting blood glucose levels among the three groups, whereas SP and captopril administration significantly suppressed the increase in blood glucose after glucose loading in the control SHRSPs. No difference was observed in plasma insulin levels among the three groups. Thus treatment with captopril and ACE-inhibitory sardine peptides ameliorated the glucose tolerance of this rat strain.

Safety Evaluation of a Peptide Product Derived From Sardine Protein Hydrolysates (Valtyron)

The peptide product, Valtyron, is obtained via enzymatic hydrolysis of sardine muscle. Although the safety and efficacy of the sardine peptide product have been evaluated in human studies, sardine peptides have not been identified as the subject of toxicological testing. In this study, the sardine peptide product did not exhibit any mutagenic activity in Salmonella typhimurium or Escherichia coli WP2uvrA. Likewise, the sardine peptide product was not associated with clastogenic properties in mouse bone marrow cells in a micronucleus assay. An oral rat LD50 value of greater than 10 000 mg per kilogram of body weight was determined for peptide α-1000, and in rats administered peptide α-1000 by gavage at levels up to 5000 mg per kilogram of body weight per day for 28 days, no compound-related differences were observed in standard toxicological parameters. The results of these studies support the safety of the sardine peptide product for use in food for human consumption as a dietary source of peptides available from sardines.