Gene/Protein Disease Symptom Drug Enzyme Compound
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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) inhibitory peptides prepared from soy protein by the action of alcalase enzyme was tested for its hypotensive effect on spontaneously hypertensive rats (SHR). Captopril, an ACE inhibitor used widely for hypertension treatment, was also applied in comparison. A significant (p < 0.05) decrease in systolic blood pressure of SHR was observed when soy ACE inhibitory peptides were orally administrated at three different dose levels (100, 500, and 1000 mg/kg of body weight/day), whereas little change occurred in the blood pressure of normotensive rats even at the highest dose. After a month-long feeding, blood pressure readings of SHR fell by approximately 38 mmHg from the original level at the lowest dose; a steadily and progressively hypotensive effect existed for these soy ACE inhibitory peptides administration groups. An obvious fluctuation was observed at the third week, although Captopril had a stronger hypotensive effect. The ACE activity of serum, aorta and lung, and lipid content of serum of SHR upon administration of soy ACE inhibitory peptides did not show a significant difference from that of the control group, whereas the serum ACE activity increased and the aorta ACE activity decreased significantly (p < 0.05) for the Captopril group. Serum Na(+) concentration decreased significantly in both the peptides-treated groups and the Captopril-treated group in comparison with the control group, whereas no lowering effect was observed for serum K(+) and serum Ca(2+) concentrations. These results suggested that the hypotensive effect of ACE inhibitory peptides derived from soy protein could be at least partly attributed to the action on salt/water balance.
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PMID:Hypotensive and physiological effect of angiotensin converting enzyme inhibitory peptides derived from soy protein on spontaneously hypertensive rats. 1117 Jun 18

We have recently demonstrated that furin, PC5, and PC7, members of the subtilisin/kexin-like mammalian proprotein convertases (PCs), are found in rodent aorta. These PCs have been identified to activate several growth factors, adhesion molecules and extracellular matrix compounds by endoproteolytic cleavage. In the present study, we investigated the regulation of PC5 in vascular smooth muscle cells (VSMCs) in vitro and in vivo. Stimulation of rat aortic VSMCs with platelet-derived growth factor (PDGF)-BB (20 ng/mL), angiotensin II (Ang II, 1 micromol/L), or 10% fetal calf serum (FCS) for 48 hours increased DNA synthesis, as assessed by proliferating cell nuclear antigen (PCNA) immunoblotting. PC5 was strongly upregulated by PDGF-BB and 10% FCS (both 8-fold, P<0.05), whereas Ang II had no effect on PC5 protein levels compared with controls. The PCs furin and PC7, which display a comparable subcellular localization and cleavage activity, were found in VSMCs, but their levels did not increase following PDGF-BB, Ang II, or FCS stimulation. Time-course analysis revealed a rapid increase in PC5 levels after 30 minutes of PDGF-stimulation of VSMCs. PDGF-stimulated PC5 induction was inhibited by the PI3-kinase inhibitor wortmannin, and by rapamycin, an inhibitor of mTOR/p70(s6)-kinase (both P<0.05). In contrast, the mitogen-activated protein kinase (MAPK)-pathway inhibitor PD98059 did not inhibit PDGF-stimulated PC5 induction. Immunocytochemistry and in situ hybridization revealed low PC5 protein and mRNA levels in intact rat aorta in vivo. After balloon injury, PC5 protein and mRNA levels were strongly increased in proliferating PCNA-positive VSMCs. The present data demonstrate that PC5 is upregulated during proliferation of VSMCs in vivo and in vitro. We show that PDGF-induced PC5 expression is PI3-kinase/p70(s6)-kinase dependent. Thus, growth factors regulate the proprotein convertase PC5, which may play an important role during VSMC growth.
Hypertension 2002 Feb
PMID:Proprotein convertase PC5 regulation by PDGF-BB involves PI3-kinase/p70(s6)-kinase activation in vascular smooth muscle cells. 1188 80

The effect of RP-HPLC-purified fractions of fish waste hydrolysates issued from three fish industries was tested on guinea pig ileum in order to examine the presence of opioid molecules. The evaluation of anti-hypertensive activities of whole hydrolysates and fractions were also tested, monitoring the ability of the fraction to inhibit the activity of angiotensin I-converting enzyme involved in hypertension regulation. Sardine autolysate and cod head hydrolysate powder (50 microg) were able to inhibit near 30% of ACE activity, whereas 50 microg of shrimp hydrolysate allows the inhibition of 57% of ACE activity. HPLC fractionation of cod head hydrolysate and sardine autolysate was necessary to evidence biological activity, whereas HPLC separation of shrimp hydrolysate exhibited low biological activity fractions. Further studies are necessary to characterise bioactive molecules from cod head alcalase hydrolysate and from sardine autolysate.
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PMID:HPLC preparation of fish waste hydrolysate fractions. Effect on guinea pig ileum and ACE activity. 1193 78

Four potent angiotensin converting enzyme (ACE) inhibitory peptides, IY, RIY, VW and VWIS, were isolated from subtilisin digest of rapeseed protein. Among them RIY and VWIS are new peptides with IC(50) 28 and 30 microM, respectively. All isolated peptides lowered blood pressure of spontaneously hypertensive rats (SHR) following oral administration. The maximum effect in the case of RIY was observed 4h after administration, while maximum effect of other peptides on blood pressure occurred 2h after administration. Furthermore, the antihypertensive effect of RIY was observed even in old rats, in which ACE inhibitors become less effective, suggesting that a different mechanism other than ACE inhibition is also involved in lowering blood pressure by this peptide. Subtilisin digest of rapeseed protein also significantly lowered blood pressure of SHR after oral administration of a single dosage 0.15 g/kg, exerting maximum antihypertensive effect 4h after administration. This digest appears promising as a functional food, which may be useful in the prevention and treatment of hypertension.
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PMID:New antihypertensive peptides isolated from rapeseed. 1294 30

The leaves of Persimmon (Diospyros kaki L.) has long been used for tea in Korea since it was thought to be effective against hypertension. An anticoagulant fraction was purified through gel filtration G-100, hydrophobic, gel filtration G-150, and FPLC, Phenyl superpose column chromatographies. The purified fraction was homogenous and its Mr was estimated 10,000 Da by gel filtration and SDS-PAGE. The purified fraction was sensitive to treatment of subtilisin B, but not to heat and its activity was not changed after periodate oxidation, indicating that the activity was not due to carbohydrates. It delayed thrombin time (TT), activated partial thromboplastin time (APTT), and prothrombin time (PT) using human plasma. TT was more sensitive than APTT and PT, suggesting that the anticoagulant activity may be caused by a degradation or a defect of fibrin or thrombin. It did not cause the hydrolysis of fibrin after incubation. However, it inhibited thrombin-catalyzed fibrin formation with a competitive inhibition pattern. These results indicate that it may be an antithrombotic agent and that it is bound to fibrinogen binding sites of thrombin.
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PMID:The anticoagulant fraction from the leaves of Diospyros kaki L. has an antithrombotic activity. 1604 75

Angiotensin I converting enzyme (ACE) inhibitory peptide was isolated from tuna dark muscle hydrolysate prepared by alcalase, neutrase, pepsin, papain, alpha-chymotrypsin, and trypsin, respectively. Among hydrolysates, the pepsin-derived hydrolysate exhibited the highest ACE I inhibitory activity versus those of other enzyme hydrolysates. The structure of the peptide was identified to be Trp-Pro-Glu-Ala-Ala-Glu-Leu-Met-Met-Glu-Val-Asp-Pro (molecular weight 1581 Da) by time of flight mass spectrometry/mass spectrometry analysis, and the IC 50 value of the peptide was 21.6 microM. The Lineweaver-Burk plots revealed that the peptide acts as a noncompetitive inhibitor, and the inhibitor constant ( K i) was calculated as 26.6 microM using the secondary plots. The peptide had an antihypertensive effect according to the time-course measurement after oral administration to spontaneously hypertensive rats. Maximal reduction was detected 3 h after oral administration at a dose of 10 mg/kg of body weight. These results suggest that the peptide derived from tuna dark muscle would be a beneficial ingredient for functional food or pharmaceuticals against hypertension and its related diseases.
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PMID:Antihypertensive effect of angiotensin i converting enzyme-inhibitory peptide from hydrolysates of Bigeye tuna dark muscle, Thunnus obesus. 1789 58

Prohormone convertase subtilisin/kexin type 1 (PCSK1) genetic polymorphisms have recently been associated with obesity in European populations. This study aimed to examine whether common PCSK1 genetic variation is associated with obesity and related metabolic phenotypes in the Chinese population. We genotyped nine common tag single-nucleotide polymorphisms (tagSNP) of the PCSK1 gene in 1,094 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) family study. One SNP in the PCSK1 gene (rs155971) were nominally associated with risk of obesity in the SAPPHIRe cohort (P = 0.01). A common protective haplotype was associated with reduced risk of obesity (23.79% vs. 32.89%, P = 0.01) and smaller waist circumference (81.71 +/- 10.22 vs. 84.75 +/- 10.48 cm, P = 0.02). Another common haplotype was significantly associated with increased risk of obesity (37.07% vs. 23.84%, P = 0.005). The global P value for haplotype association with obesity was 0.02. We also identified a suggestive association of another PCSK1 SNP (rs3811951) with fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA(IR)), triglycerides, and high-density lipoprotein cholesterol (P = 0.05, 0.003, 0.001, 0.04, and 0.04, respectively). These data indicate common PCSK1 genetic variants are associated with obesity in the Chinese population.
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PMID:Common PCSK1 haplotypes are associated with obesity in the Chinese population. 1987 84

This study aims to identify peptides with angiotensin-I converting enzyme (ACE) inhibitory activity in hydrolysate from chicken leg bone protein hydrolyzed with alcalase for 4 h (A4H). The hydrolysate has demonstrated potent in vitro ACE inhibitory activity, and has been shown to attenuate the development of hypertension and cardiovascular hypertrophy in spontaneously hypertensive rats (SHR). A4H is competitive for ACE and was separated using high-performance liquid chromatography (HPLC) with a gel filtration column (Superdex Peptide HR 10/30). The results show that A4H is a mixed non-competitive inhibitor. Eighteen fractions were detected after separation of A4H, and most of them showed ACE inhibitory activity. Five fractions with strong ACE inhibitory activities (above 50%) were labeled from A to E. In addition, there were 10 peptides, consisting of 5-10 amino acid residues that were identified from fraction D that exhibited the strongest ACE inhibitory activity. Three of the identified peptides corresponded to peptides derived from collagen type I and chicken muscular protein. It is revealed that A4H has several peptides that possess ACE inhibitory activities.
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PMID:Determination of angiotensin-I converting enzyme inhibitory peptides in chicken leg bone protein hydrolysate with alcalase. 2016 74

An angiotensin I-converting enzyme (ACE) inhibitory peptide Ile-Gln-Pro with an IC(50) value of 5.77 +/- 0.09 microM was purified from the alcalase digests of Spirulina platensis by gel filtration chromatography and two steps of reverse-phase high-performance liquid chromatography (RP-HPLC). The peptide was synthesized and showed resistance to in vitro digestion by gastrointestinal proteases. Kinetics studies indicated that the peptide was a noncompetitive inhibitor and that the K(i) value was 7.61 +/- 0.16 microM. Oral administration of Ile-Gln-Pro at a dosage of 10 mg/kg showed significant decreases of the weighted systolic blood pressure (SBP) and diastolic blood pressure (DBP) in spontaneously hypertensive rats (SHR) at 4, 6, and 8 h after treatment. The results showed that the ACE inhibitory peptide from Spirulina platensis may have potential for use in the prevention and treatment of hypertension.
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PMID:Isolation of an antihypertensive peptide from alcalase digest of Spirulina platensis. 2050 91

A peptide possessing antihypertensive activity was purified from Nile tilapia ( Oreochromis niloticus ) gelatin using alcalase, Pronase E, pepsin, and trypsin. Among them, the alcalase hydrolysate exhibited the highest angiotensin converting enzyme (ACE) inhibitory activity. Therefore, it was further analyzed, and a potent ACE inhibitory peptide of DPALATEPDPMPF (1382 Da) was separated and purified. In addition, the protective effect of the purified peptide against free radical-induced cellular and DNA damage in murine microglial cells (BV-2) was determined. These results suggest that the peptide isolated from Nile tilapia (O. niloticus) gelatin acts as a candidate against hypertension and oxidative stress and could be used in health-functional foods.
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PMID:An antihypertensive peptide from tilapia gelatin diminishes free radical formation in murine microglial cells. 2200 28


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