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

Abstract

1. Intact absorption of the bioactive dipeptide Val-Tyr (VY), with in vivo antihypertensive ability in normotensive human subjects, was investigated. 2. As a result of a single oral administration of VY, the VY absorption curve occurred maximally over the second hour postprandially; a greater than 10-fold higher increment of VY following a dose of 12 mg was observed in the plasma at 2 h compared with the baseline concentration of VY at 0 h (1934 +/- 145 vs 159 +/- 11 fmol/mL plasma, respectively). 3. Plasma VY levels increased with dose administered (3, 6 and 12 mg), suggesting that exogenous VY could be absorbed intact into the human blood depending on the dose. The elimination half time (t1/2) of VY was estimated to be 3.1 h. The area under the curve for the 12 mg VY dose was 9185 +/- 688 fmol small middle doth/mL plasma.

Absorption of Val-Tyr with in Vitro Angiotensin I-Converting Enzyme Inhibitory Activity into the Circulating Blood System of Mild Hypertensive Subjects.

“…Net AUC (area under the curve over 24 h) for a 12 mg VY-dose calculated from overall AUC minus AUC for endogenous VY showed a 1.3 times higher absorption than that of a 6 mg VY-dose. Interestingly, all of the pharmacokinetics of VY in the mild hypertensive subjects were in good agreement with those in normotensive subjects (12 mg of VY dosage: C max ; 1934Ϯ145 fmol/ml-plasma, T max ; 2 h, AUC; 9185Ϯ688 fmol · h/ml-plasma 13) ). To date, a human peptide transporter, PepT1, expressed primarily in the small intestine has been cloned as a proton-dependent transporter peptide.…”

“…These findings led us to investigate how much amount of VY can be absorbed in a single oral administration by mild hypertensive subjects. In our previous paper, 13) intact VY absorption with pmol level per ml-plasma was identified in normotensive human subjects. It remains unclear, however, whether VY as a natural angiotensin I-converting enzyme (ACE) inhibitor with the IC 50 value of 26 mM 14) can be absorbed and can exert an acute hypotensive power as can a therapeutic drug in hypertensive subjects.…”

Casein-Derived Tripeptide, Val-Pro-Pro (VPP), Modulates Monocyte Adhesion to Vascular Endothelium

“…Among ACE inhibitory peptides, IPP, VPP [35][36][37] and VY 38,39) are shown to be absorbed in part through the intestine, enter the systemic circulation without significant degradation, and then exert bioactive properties at the tissue level. Previously, casein hydrolysate containing VPP and IPP improved vascular endothelial dysfunction in subjects with mild hypertension independent of the change in systemic blood pressure 14) .…”

Determination of Antihypertensive Small Peptides, Val-Tyr and Ile-Val-Tyr, by Fluorometric High-Performance Liquid Chromatography Combined with a Double Heart-Cut Column-Switching Technique

“…14,15 However, few applications of NDA to peptide-derivatization have been reported, except for VY 13 and Gly-Gly-Gly. 16 Therefore, the optimal reaction conditions of VY and IVY with NDA were examined.…”

“…After an immediate centrifugation at 3500g for 15 min (4˚C), 10 mM aprotinin (Sigma-Aldrich, St. Louis, MO, USA), 20 mM chymostatin (Sigma-Aldrich), and 1 mM EDTA-2Na were added to the obtained plasma to avoid any excess hydrolyses by plasma peptidases. 13 Then, 0.5 mL 10% (w/v) trichloroacetic acid was added to 1.0-mL plasma sample to remove proteins, followed by a centrifugation at 10000g for 20 min (4˚C). Then, a solid-phase extraction of the supernatant with a Sep-Pak Plus C18 cartridge (Waters, Milford, Massachusetts, USA) was performed.…”