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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin-converting enzyme (ACE) is important in the regulation of blood pressure (BP). Two tripeptides that inhibit ACE, isoleucyl-prolyl-proline (Ile-Pro-Pro) and valyl-prolyl-proline (Val-Pro-Pro), have been isolated from certain sour milks. The aim of the study reported was to evaluate the effect on BP in subjects with mild hypertension of a new sour milk containing tripeptides. The initial number of subjects was 60 (36 men, 24 women). Among the criteria for inclusion in the study were systolic BP (SBP) between 140 and 180 mmHg and/or diastolic BP (DPB) between 90 and 110 mmHg, without antihypertensive drug therapy. There were two study periods with a washout period between. All subjects were given 1.5 dl per day of a placebo (regular sour milk) or of the active product, a milk that had been fermented with Lactobacillus helveticus bacteria and contained 2.4-2.7 mg of Ile-Pro-Pro and 2.4-2.7 mg of Val-Pro-Pro per 1.5 dl. In the first phase, SBP fell 16 mmHg from baseline in the active group, 2 mmHg more than in the placebo group (P=0.0668) and no difference in DBP (P=0.92). There was a statistically significant downward trend both in SBP and DBP (P=0.0001). During the second phase, SBP fell 11 mmHg in the active group (P=0.008). The reduction in SBP was significantly larger in active than placebo group (P=0.012). In the crossover analysis combining both phases, SBP fell on average 2.6+/-15.9 mmHg more on the active product compared with the placebo product, but this difference was not statistically significant (P=0.3111). The difference in DBP, 1.0+/-8.3 mmHg between the two test products was not significant either (P=0.4431). In conclusion, the ingestion of sour milk fermented by L. helveticus bacteria and that containing ACE inhibitory tripeptides seems to lower BP modestly.
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PMID:Effect of ingesting sour milk fermented using Lactobacillus helveticus bacteria producing tripeptides on blood pressure in subjects with mild hypertension. 1517 33

The development of renin inhibitors for the treatment of hypertension requires highly sensitive substrates to evaluate potency and to characterize the mechanism of tight-binding inhibitors. A series of intramolecularly quenched fluorogenic renin substrates, based on the N-terminal tetradecapeptide sequence of human angiotensinogen (hTDP), was synthesized using a solid-phase technique. Incorporation of the fluorescent amino acid L-Amp [L-2-amino-3-(7-methoxy-4-coumaryl)propionic acid] and the DNP (2,4-dinitrophenyl) group at various positions resulted in >90% quenching efficiency and strong product fluorescence. Shortening the hTDP sequence to an octapeptide from histidine in P5 to histidine in P3' (substrate 3) resulted in an acceptable k(cat)/K(m) (41000 M(-1).s(-1)) and further systematic variation gave substrate 9, DNP-Lys-His-Pro-Phe-His-Leu-Val-Ile-His-L-Amp, with a k(cat)/K(m) value of 350000 M(-1).s(-1) and 94% quenching efficiency. The free side chain of lysine, replacing the isoleucine residue at P6 position in the angiotensinogen sequence, contributed to the increased value for k(cat). The pH dependence of k(cat)/K(m) for renin and substrate 9 showed that the optimal pH is at pH 6-7. It also showed two titrating groups on the acidic side of the pH optimum, and one titrating group with a pK(a) of 7.8 on the alkaline side. The combination of good kinetic and spectroscopic properties resulted in a >20-fold improvement in the sensitivity of renin assay, compared with the commercial substrate Arg-Glu(EDANS)-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Thr-Lys(DABCYL)-Arg [where EDANS is 5-[(2-aminoethyl)amino]naphthalene-1-sulphonic acid and DABCYL is 4-(4-dimethylaminophenylazo)benzoic acid] (k(cat)/K(m)=268000 M(-1) x s(-1), quenching efficiency <80%). The detection limit in a microplate renin assay was 60 pM, making substrate 9 well suited for the evaluation of inhibitors at picomolar concentrations.
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PMID:Highly sensitive intramolecularly quenched fluorogenic substrates for renin based on the combination of L-2-amino-3-(7-methoxy-4-coumaryl)propionic acid with 2,4-dinitrophenyl groups at various positions. 1523 25

This work reports the antioxidant activity of peptides produced by enzymatic hydrolysis of crude egg white with pepsin. Four peptides included in the protein sequence of ovalbumin possessed radical scavenging activity higher than that of Trolox. The hydrolysate of egg white with pepsin for 3 h was previously found to exhibit a strong angiotensin I-converting enzyme (ACE) inhibitory activity in vitro. The combined antioxidant and ACE inhibition properties make it a very useful multifunctional preparation for the control of cardiovascular diseases, particularly hypertension. No correlation was found between antioxidant and ACE inhibitory activities. However, the peptide Tyr-Ala-Glu-Glu-Arg-Tyr-Pro-Ile-Leu, which was a strong ACE inhibitor (50% inhibitory concentration, 4.7 microM) also exhibited a high radical scavenging activity (oxygen radical absorbance capacity-fluorescein value, 3.8 micromol of Trolox equivalent per micromol of peptide) and delayed the low-density lipoprotein lipid oxidation induced by Cu2+ at a concentration of approximately 0.16 mg/mg of low-density lipoprotein. Present results support that antioxidant peptides and amino acids not only act individually, but also cooperatively and synergistically.
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PMID:Antioxidant activity of peptides derived from egg white proteins by enzymatic hydrolysis. 1545 85

Previously, a blood pressure (BP) quantitative trait locus (QTL) on rat chromosome 9 (RNO9) was localized to a <2.4 cM interval using congenic strains generated by introgressing segments of RNO9 from the Dahl salt-resistant (R) rat into the background of the Dahl salt-sensitive (S) rat. Renal gene expression using Affymetrix gene chips was profiled on S and a congenic strain spanning the 2.4-cM BP QTL interval. This analysis identified 20 differentially expressed genes/expressed sequence tags. Of these, the locus with the greatest differential expression (30- to 35-fold) was regulated endocrine-specific protein 18 (Resp18), which also mapped in the 2.4-cM BP QTL interval. Additional substitution mapping located the QTL to <0.4 cM or approximately 493 kb. This newly defined QTL region still included Resp18. Nucleotide variants were identified between S and R genomic DNA of Resp18 in the coding, 5' regulatory and 3' untranslated regions. The coding sequence variation (T/C) occurs in exon 2 and predicts an amino acid change (Ile/Val) in the protein product. Resp18 was considered a differentially expressed positional candidate for the QTL. To fine-map the BP QTL, we constructed a congenic strain with a smaller introgressed region. Compared with the S rat, this strain (1) had significantly lower BP, (2) did not contain the R form of Resp18, and (3) did not retain the rather spectacular differential expression of Resp18. Together, these results demonstrate that a BP QTL independent of Resp18 exists within the newly defined 117-kb QTL region on RNO9.
Hypertension 2005 Mar
PMID:Locating a blood pressure quantitative trait locus within 117 kb on the rat genome: substitution mapping and renal expression analysis. 1621 81

We investigated the role of angiotensin II type 1 (AT1) and AT2 receptors, matrix metalloproteinases (MMPs), and extracellular matrix (ECM) components involved in vascular remodeling of resistance arteries induced by angiotensin II (Ang II). Sprague-Dawley rats received Ang II (120 ng/kg per minute SC) +/- the AT1 antagonist losartan (10 mg/kg per day PO), the AT1/AT2 antagonist Sar1-Ile8-Ang II (Sar-Ile; 10 microg/kg per minute SC), or hydralazine (25 mg/kg per day PO) for 7 days. Structure and mechanical properties of small mesenteric arteries were evaluated on a pressurized myograph. Ang II increased growth index (+21%), which was partially decreased by losartan (-11%) and abrogated by Sar-Ile. Hydralazine markedly increased growth index (+32%) despite systolic blood pressure (BP) lowering, suggesting a BP-independent effect of Ang II on vascular growth. Elastic modulus was increased by Sar-Ile compared with Ang II and control. Vascular type I collagen was reduced (P<0.05), whereas fibronectin increased significantly with Sar-Ile. Vascular tissue inhibitor of metalloproteinase-2 binding to MMP-2 was abrogated by Sar-Ile, but MMP-2 activity was significantly increased compared with losartan, Ang II, and controls. Thus, AT1 blockade exerted antigrowth effects and reduced stiffness of small resistance arteries by decreasing nonelastic fibrillar components (collagen and fibronectin). Concomitant AT1/AT2 blockade prevented growth, reduced collagen type I and elastin deposition but increased vascular stiffness, fibronectin, and MMP-2 activity. These results demonstrate opposing roles of AT1 receptors that increase fibronectin and vascular stiffness and AT2 receptors that decrease MMP-2 and increase elastin. Changes in vascular wall mechanics, ECM deposition, and MMP activity are thus modulated differentially by Ang II receptors.
Hypertension 2005 Sep
PMID:Combined angiotensin II type 1 and type 2 receptor blockade on vascular remodeling and matrix metalloproteinases in resistance arteries. 1604 61

We describe a clinical trial to study the efficacy of a casein hydrolysate, prepared using an Aspergillus oryzae protease, containing the major angiotensin-I-converting enzyme inhibitory peptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) in a single-blind, placebo-controlled study. A total of 131 volunteers with high-normal blood pressure and mild hypertension were randomly divided into four groups (n 32 or 33 in each group). Each volunteer was given two tablets containing four different dosages of VPP and IPP (VPP+IPP: 0, 1.8, 2.5 and 3.6 mg), daily for 6 weeks. A significant decrease in systolic blood pressure was observed at 6 weeks in the active group receiving 1.8 mg (P<0.01) VPP and IPP; in the active groups receiving either 2.5 mg or 3.6 mg, systolic blood pressure was decreased at both 3 weeks (P<0.05 and P<0.05) and 6 weeks (P<0.001 and P<0.0001) compared with systolic blood pressure measured before treatment. Changes in the systolic blood pressure after 6 weeks of treatment in the four groups were --1.7, --6.3, --6.7 and --10.1 mmHg, and these effects were dose dependent. In addition, a significant difference in systolic blood pressure between the placebo group and the VPP and IPP group receiving 3.6 mg was observed (P<0.001) by two-way ANOVA. The antihypertensive effect was greater in mildly hypertensive subjects (n 20 or 21 in each group) than in any of the other subjects. No significant change of diastolic blood pressure was observed for all the test groups, and no differences in diastolic blood pressure in the test sample groups compared with the placebo group were observed during the test period.
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PMID:Antihypertensive effect of casein hydrolysate in a placebo-controlled study in subjects with high-normal blood pressure and mild hypertension. 1611 37

In the present study we evaluate the blood pressure-lowering effect of the following products: the hydrolysate obtained from egg white (EW) by enzymatic treatment with pepsin (HEW), the peptide fraction of HEW with molecular mass lower than 3000 Da (HEW<3000 Da), and three peptide sequences isolated from HEW<3000 Da (Tyr-Ala-Glu-Glu-Arg-Tyr-Pro-Ile-Leu: YAEERYPIL); (Arg-Ala-Asp-His-Pro-Phe-Leu: RADHPFL); and (Ile-Val-Phe (IVF)). These peptides, and also HEW and HEW<3000 Da, had been characterized previously in vitro as potent inhibitors of angiotensin-converting enzyme (ACE). EW and the products mentioned earlier were orally administered by gastric intubation, to 17-20-week-old male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. We measured the systolic blood pressure (SBP) and the diastolic blood pressure (DBP) of the rats by the tail cuff method before administration and also 2, 4, 6, 8 and 24 h post-administration. Distilled water served as negative control, and we used captopril (50 mg/kg) as positive control to carry out similar experiments with a known ACE inhibitor. HEW, HEW<3000 Da and the three peptide sequences decreased SBP and DBP in SHR but they did not modify these variables in WKY rats. The peptide sequences YAEERYPIL, RADHPFL and IVF showed a potency to decrease blood pressure greater than HEW or HEW<3000 Da. The results obtained suggest that the studied products could be used as a functional food with potential therapeutic benefit in the prevention and treatment of hypertension.
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PMID:Short-term effect of egg-white hydrolysate products on the arterial blood pressure of hypertensive rats. 1627 76

Casein hydrolysate, prepared with Aspergillus oryzae protease, contains angiotensin I-converting enzyme inhibitory peptides, such as Val-Pro-Pro and Ile-Pro-Pro. We conducted a randomized, double-blind, placebo-controlled study to evaluate the effect of casein hydrolysate on the blood pressure of 144 subjects with high-normal blood pressure (n = 104) and mild hypertension (n = 40). Subjects were randomly assigned to two groups for a 12-week intake period. In the test group, both systolic (SBP) and diastolic (DBP) blood pressure decreased significantly compared with the placebo group: SBP/DBP significantly decreased from 138.2 +/- 6.5/84.4 +/- 5.3 mm Hg at week 0 to 132.3 +/- 7.3 (P < .001)/81.2 +/- 4.8 mm Hg (P < .001) at week 12. In the stratified analysis, the test product showed an antihypertensive effect in both the subject group with high-normal blood pressure and that with mild hypertension. No side effect was observed in any subjects in this study. These results demonstrate that the casein hydrolysate, prepared with A. oryzae protease, produced a significant reduction in blood pressure in a population of subjects with high-normal blood pressure or mild hypertension without an adverse event.
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PMID:Effect of casein hydrolysate, prepared with protease derived from Aspergillus oryzae, on subjects with high-normal blood pressure or mild hypertension. 1637 51

There have been studies of antihypertensive peptides derived from food proteins, but very few described the production of bioactive peptides from egg proteins. The first 2 antihypertensive peptides isolated in egg were obtained by enzymatic hydrolysis of ovalbumin. They correspond to the sequences Phe-Arg-Ala-Asp-His-Pro-Phe-Leu (ovokinin) and Arg-Ala-Asp-His-Phe-Leu (ovokinin 2-7). Both exhibited endothelium-dependent vasodilatory activity. Ovokinin (2-7) had higher antihypertensive potency than ovokinin in spontaneously hypertensive rats (SHR). Modifications in the sequence of ovokinin (2-7) improved the bioavailability of this peptide. It was also demonstrated that different ovalbumin hydrolysates can inhibit angiotensin I-converting enzyme (ACE). We recently obtained an egg white hydrolysate that inhibited the enzyme in vitro. It was obtained by treating egg white with pepsin and it exhibited antihypertensive activity in SHR. Some ACE-inhibitory peptides obtained from this hydrolysate (Tyr-Arg-Glu-Glu-Arg-Tyr-Pro-Ile-Leu, Arg-Ala-Asp-His-Pro-Phe-Leu, and Ile-Val-Phe) also showed antihypertensive activity in these rats. The egg products mentioned could be used as functional food ingredients with potential therapeutic benefit in the prevention and treatment of hypertension.
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PMID:Antihypertensive peptides derived from egg proteins. 1670 3

Sesame peptide powder (SPP) exhibited angiotensin I-converting enzyme (ACE) inhibitory activity, and significantly and temporarily decreased the systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) by a single administration (1 and 10 mg/kg). Six peptide ACE inhibitors were isolated and identified from SPP. The representative peptides, Leu-Val-Tyr, Leu-Gln-Pro and Leu-Lys-Tyr, could competitively inhibit ACE activity at respective Ki values of 0.92 microM, 0.50 microM, and 0.48 microM. A reconstituted sesame peptide mixture of Leu-Ser-Ala, Leu-Gln-Pro, Leu-Lys-Tyr, Ile-Val-Tyr, Val-Ile-Tyr, Leu-Val-Tyr, and Met-Leu-Pro-Ala-Tyr according to their content ratio in SPP showed a strong antihypertensive effect on SHR at doses of 3.63 and 36.3 microg/kg, which accounted for more than 70% of the corresponding dosage for the SPP-induced hypotensive effect. Repeated oral administration of SPP also lowered both SBP and the aortic ACE activity in SHR. These results demonstrate that SPP would be a beneficial ingredient for preventing and providing therapy against hypertension and its related diseases.
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PMID:Antihypertensive effect of angiotensin I-converting enzyme inhibitory peptides from a sesame protein hydrolysate in spontaneously hypertensive rats. 1671 11


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