ABSTRACT
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.
Subject(s)
Antihypertensive Agents/therapeutic use , Dipeptides/therapeutic use , Hypertension/drug therapy , Adult , Aldosterone/blood , Angiotensin I/blood , Angiotensin II/blood , Animals , Double-Blind Method , Female , Fishes/metabolism , Humans , Hydrolysis , Hypertension/physiopathology , Male , Middle Aged , Muscles/metabolism , Reference ValuesABSTRACT
A survey of food components with alpha-glucosidase (AGH) inhibitory activity was conducted to identify a prophylactic effect for diabetes in food. Sardine muscle hydrolyzed by alkaline protease showed potent activity (IC50 = 48.7 mg/ml) as well as green and oolong teas (IC50 = 11.1 and 11.3 mg/ml, respectively). Furthermore, hydrolyzates prepared by various proteases gave differing AGH inhibitory activity. DEAE-Sephadex chromatography of the alkaline protease hydrolyzate eluted potent AGH inhibitors (IC50 = 15.6 mg/ml) with a 50 mM phosphate buffer (pH 7.0) containing 0.3 M NaCl, and their subsequent separation by HPLC in an ODS column showed that there were some inhibitors possessing primary amino groups. This indicates that they would have been high anionic and peptidic compounds.
Subject(s)
Enzyme Inhibitors/analysis , Food Analysis , Glycoside Hydrolase Inhibitors , Animals , Chromatography, DEAE-Cellulose , Chromatography, High Pressure Liquid , Enzyme Inhibitors/isolation & purification , Enzyme Inhibitors/pharmacology , Fishes , Intestinal Mucosa/drug effects , Intestinal Mucosa/enzymology , Muscles/enzymology , Protein Hydrolysates/analysis , Protein Hydrolysates/pharmacology , Tea/chemistryABSTRACT
When angiotensin fragments, Val-Tyr and Angiotensin III (ANG III), with potent ACE inhibitory activity were intravenously administered to spontaneously hypertensive rat (SHR), a significant reduction of diastolic blood pressure was observed. After incubation of ANG III with SHR plasma, four fragments with ACE inhibitory activity, Val-Tyr (ANG (3-4)) (IC50 = 26.0 microM), Ile-His-Pro-Phe (ANG (5-8)) (11.6 microM), Tyr-Ile-His-Pro-Phe (ANG (4-8)) (457.5 microM), and Val-Tyr-Ile-His-Pro-Phe (ANG (3-8)) (6.55 microM), were confirmed to generate in SHR plasma. Compared the metabolic behavior of ANG II in SHR plasma with that in normotensive Wistar plasma, the initial degradation rate (3.07 nmol/ml/min) in Wistar plasma was about 2-fold higher than that in the SHR one (1.75 nmol/ml/min).
Subject(s)
Angiotensin III/pharmacology , Angiotensin II/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Antihypertensive Agents/pharmacology , Peptide Fragments/pharmacology , Amino Acid Sequence , Angiotensin II/metabolism , Animals , Blood Pressure , Hypertension , Male , Molecular Sequence Data , Peptidyl-Dipeptidase A/metabolism , Rats , Rats, Inbred SHR , Structure-Activity RelationshipABSTRACT
We conducted a prospective study to clarify mortality patterns among Japanese coal miners in a former coal mining area. Subjects included 1,796 coal miners and 4,022 non-coal-miners, who were identified by a mail survey between 1987 and 1989, and then followed up from the date of the survey to April 30th, 1994. We applied Cox's proportional hazards model to compare the mortalities between coal miners and non-coal-miners. Among the coal miners, significantly high risk ratios were observed in all causes of death (risk ratio = 1.4, p < 0.05) and all malignant neoplasms (risk ratio = 1.5, p < 0.05). Risk ratios for all causes of death and all malignant neoplasms also rose with the length of experience in coal mining. Analysis of the results for sites of cancer showed that coal miners had high risk ratios for stomach cancer (risk ratio = 1.6), liver cancer (risk ratio = 1.4) and lung cancer (risk ratio = 1.6), though these ratios were not statistically significant. When the risk ratio for lung cancer was analyzed according to the length of experience in coal mining, coal miners with at least 15 years' experience had a significantly high risk ratio (risk ratio = 2.4, p < 0.05), though coal miners with less than 15 years' experience had almost the same risk as non-coal-miners.
Subject(s)
Coal Mining , Neoplasms/mortality , Occupational Diseases/mortality , Adult , Aged , Cause of Death , Humans , Japan/epidemiology , Male , Middle Aged , Prospective StudiesABSTRACT
The ACE inhibitory activity of an alkaline protease hydrolyzate from sardine muscle did not change after being treated by gastrointestinal proteases (IC50 = 0.082 mg protein/ml). Eleven new ACE inhibitory peptides, constructed with 2 to 4 amino acid residues, were isolated from the hydrolyzate. The ACE inhibitory activity of each was mostly below 100 microM of IC50 value; the maximal inhibitory activity was observed for Lys-Trp (IC50 = 1.63 microM). The isolated peptides inhibited ACE competitively, except for Met-Tyr with non-competitive inhibition. As the result of sequence homology, Arg-Val-Tyr isolated from the hydrolyzate was found in the primary structure of angiotensins I, II, and III, and of des As[1]-angiotensin I.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/isolation & purification , Endopeptidases/chemistry , Peptides/isolation & purification , Peptidyl-Dipeptidase A/metabolism , Amino Acid Sequence , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Fishes , Hydrogen-Ion Concentration , Hydrolysis , Molecular Sequence Data , Muscles/enzymology , Peptides/pharmacologyABSTRACT
Hydrolyzates which inhibit the angiotensin I-converting enzyme (ACE) were prepared from sardine muscle by Bacillus licheniformis alkaline protease. Considering the practical application of preparations as a functional food material, the best proteolytic conditions with respect to taste, solubility and ACE inhibitory activity were a 0.3 wt% addition of the enzyme and 17-h proteolysis at 50 degrees C and pH 9.0. The preparations under these conditions had potent activity (IC50 = 0.26 mg protein/ml). Fractionation of the preparations on an ODS column with ethanol resulted in the production of more potent inhibitors. The most potent activity was obtained when eluting with 10% ethanol (IC50 = 0.015 mg protein/ml). This fraction was apparently rich in acidic amino acids, poor in hydrophobic ones, and effective for use as a physiologically functional food material by virtue of little bitterness, a fish odor and powerful ACE inhibitory activity.
