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Effects of Angiotensin 1-7 and Mas Receptor Agonist on Renal System in a Rat Model of Heart Failure.International Journal of Molecular... Jul 2023Congestive heart failure (CHF) is often associated with impaired kidney function. Over- activation of the renin-angiotensin-aldosterone system (RAAS) contributes to avid...
Congestive heart failure (CHF) is often associated with impaired kidney function. Over- activation of the renin-angiotensin-aldosterone system (RAAS) contributes to avid salt/water retention and cardiac hypertrophy in CHF. While the deleterious effects of angiotensin II (Ang II) in CHF are well established, the biological actions of angiotensin 1-7 (Ang 1-7) are not fully characterized. In this study, we assessed the acute effects of Ang 1-7 (0.3, 3, 30 and 300 ng/kg/min, IV) on urinary flow (UF), urinary Na excretion (UNaV), glomerular filtration rate (GFR) and renal plasma flow )RPF) in rats with CHF induced by the placement of aortocaval fistula. Additionally, the chronic effects of Ang 1-7 (24 µg/kg/h, via intra-peritoneally implanted osmotic minipumps) on kidney function, cardiac hypertrophy and neurohormonal status were studied. Acute infusion of either Ang 1-7 or its agonist, AVE 0991, into sham controls, but not CHF rats, increased UF, UNaV, GFR, RPF and urinary cGMP. In the chronic protocols, untreated CHF rats displayed lower cumulative UF and UNaV than their sham controls. Chronic administration of Ang 1-7 and AVE 0991 exerted significant diuretic, natriuretic and kaliuretic effects in CHF rats, but not in sham controls. Serum creatinine and aldosterone levels were significantly higher in vehicle-treated CHF rats as compared with controls. Treatment with Ang 1-7 and AVE 0991 reduced these parameters to comparable levels observed in sham controls. Notably, chronic administration of Ang 1-7 to CHF rats reduced cardiac hypertrophy. In conclusion, Ang 1-7 exerts beneficial renal and cardiac effects in rats with CHF. Thus, we postulate that ACE2/Ang 1-7 axis represents a compensatory response to over-activity of ACE/AngII/AT1R system characterizing CHF and suggest that Ang 1-7 may be a potential therapeutic agent in this disease state.
Topics: Rats; Animals; Heart Failure; Kidney; Angiotensin I; Peptide Fragments; Cardiomegaly; Renin-Angiotensin System; Angiotensin II
PubMed: 37511227
DOI: 10.3390/ijms241411470 -
Journal of Clinical Medicine Jul 2023Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous condition predominantly affecting autonomic control of the cardiovascular system. Its extensive...
BACKGROUND
Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous condition predominantly affecting autonomic control of the cardiovascular system. Its extensive symptom diversity implies multi-organ involvement that interacts in ways still requiring full exploration. Current understanding of POTS pathophysiology suggests alterations in the renin-angiotensin-aldosterone system as a possible contributing factor. Therefore, we investigated the relationship between the activity of the renin-angiotensin-aldosterone system and hemodynamic parameters in a cohort of POTS patients and controls recruited at a tertiary referral center.
METHODS
The case-control study included 46 patients with POTS (27 ± 9 years), and 48 healthy controls (30 ± 9 years) without orthostatic intolerance. Plasma renin activity, expressed as angiotensin I generation, and plasma aldosterone were measured by enzyme-linked immunosorbent assay and were correlated with hemodynamic parameters obtained during active standing tests.
RESULTS
Renin activity was significantly downregulated in POTS patients compared to healthy individuals (median, 3406 ng/mL vs. 9949 ng/mL, < 0.001), whereas aldosterone concentration did not differ between POTS and healthy controls (median, 218 pmol/L vs. 218 pmol/L, = 0.26). A significant inverse correlation between renin activity and supine and orthostatic blood pressure levels was observed in healthy individuals ( < 0.05 for all), but not in POTS patients.
CONCLUSIONS
Renin activity, but not aldosterone concentration, is downregulated in patients with POTS. Moreover, renin activity in POTS is dissociated from supine and standing blood pressure levels in contrast to healthy individuals. These findings suggest impaired renin function in POTS, which may direct future therapeutic approaches.
PubMed: 37510775
DOI: 10.3390/jcm12144660 -
Frontiers in Nutrition 2023Exceeding 50% tuna catches are regarded as byproducts in the production of cans. Given the high amount of tuna byproducts and their environmental effects induced by...
BACKGROUND
Exceeding 50% tuna catches are regarded as byproducts in the production of cans. Given the high amount of tuna byproducts and their environmental effects induced by disposal and elimination, the valorization of nutritional ingredients from these by-products receives increasing attention.
OBJECTIVE
This study was to identify the angiotensin-I-converting enzyme (ACE) inhibitory (ACEi) peptides from roe hydrolysate of Skipjack tuna () and evaluate their protection functions on HO-induced human umbilical vein endothelial cells (HUVECs).
METHODS
Protein hydrolysate of tuna roes with high ACEi activity was prepared using flavourzyme, and ACEi peptides were isolated from the roe hydrolysate using ultrafiltration and chromatography methods and identified by ESI/MS and Procise Protein/Peptide Sequencer for the N-terminal amino acid sequence. The activity and mechanism of action of isolated ACEi peptides were investigated through molecular docking and cellular experiments.
RESULTS
Four ACEi peptides were identified as WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12), respectively. The affinity of WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) with ACE was -8.590, -9.703, -9.325, and -8.036 kcal/mol, respectively. The molecular docking experiment elucidated that the significant ACEi ability of WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) was mostly owed to their tight bond with ACE's active sites/pockets via hydrophobic interaction, electrostatic force and hydrogen bonding. Additionally, WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) could dramatically elevate the Nitric Oxide (NO) production and bring down endothelin-1 (ET-1) secretion in HUVECs, but also abolish the opposite impact of norepinephrine (0.5 μM) on the production of NO and ET-1. Moreover, WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) could lower the oxidative damage and apoptosis rate of HO-induced HUVECs, and the mechanism indicated that they could increase the content of NO and activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) to decrease the generation of reactive oxygen species (ROS) and malondialdehyde (MDA).
CONCLUSION
WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) are beneficial ingredients for healthy products ameliorating hypertension and cardiovascular diseases.
PubMed: 37502715
DOI: 10.3389/fnut.2023.1197382 -
Journal of the... 2023All strains of SARS-CoV-2, as well as previously described SARS-CoV and MERS-CoV, bind to ACE2, the cell membrane receptor of -coronaviruses. Monocarboxypeptidase ACE2... (Review)
Review
All strains of SARS-CoV-2, as well as previously described SARS-CoV and MERS-CoV, bind to ACE2, the cell membrane receptor of -coronaviruses. Monocarboxypeptidase ACE2 activity stops upon viral entry into cells, leading to inadequate tissue production of angiotensin 1-7 (Ang1-7). Acute lung injury due to the human respiratory syncytial virus (hRSV) or avian influenza A H7N9 and H5N1 viruses is also characterized by significant downregulation of lung ACE2 and increased systemic levels of angiotensin II (Ang II). Restoration of Ang1-7 anti-inflammatory, antifibrotic, vasodilating, and natriuretic properties was attempted at least in some COVID-19 patients through i.v. infusion of recombinant human ACE2 or intranasal administration of the modified ACE2 protein, with inconsistent clinical results. Conversely, use of ACE inhibitors (ACEis), which increase ACE2 cell expression, seemed to improve the prognosis of hypertensive patients with COVID-19. To restore Ang1-7 tissue levels in all these viral diseases and avoid the untoward effects frequently seen with ACE2 systemic administration, a different strategy may be hypothesized. Experimentally, when metallopeptidase inhibitors block ACE2, neprilysin (NEP), highly expressed in higher and lower airways, starts cleaving angiotensin I (Ang I) into Ang1-7. We suggest a discerning use of ACEis in normohypertensive patients with -coronavirus disease as well as in atypical pneumonia caused by avian influenza viruses or hRSV to block the main ACE-dependent effects: Ang II synthesis and Ang1-7 degradation into angiotensin 1-5. At the same time, i.v.-infused Ang I, which is not hypertensive provided ACE is inhibited, may become the primary substrate for local Ang1-7 synthesis via ubiquitous NEP; i.e., NEP could replace inadequate ACE2 function if Ang I was freely available. Moreover, inhibitors of chymase, a serine endopeptidase responsible for 80% of Ang II-forming activity in tissues and vessel walls, could protect patients with atypical pneumonia from Ang II-mediated microvascular damage without reducing arterial blood pressure.
Topics: Animals; Humans; Renin-Angiotensin System; COVID-19; SARS-CoV-2; Peptidyl-Dipeptidase A; Angiotensin-Converting Enzyme 2; Influenza A Virus, H5N1 Subtype; Influenza A Virus, H7N9 Subtype; Angiotensin-Converting Enzyme Inhibitors; Angiotensin II; Hypertension
PubMed: 37476705
DOI: 10.1155/2023/3362391 -
Molecules (Basel, Switzerland) Jul 2023Atlantic sea cucumber is a benthic marine echinoderm found in Northwest Atlantic waters and is harvested mainly for its body wall. The body wall, along with internal...
Atlantic sea cucumber is a benthic marine echinoderm found in Northwest Atlantic waters and is harvested mainly for its body wall. The body wall, along with internal organs and aquaphyrangeal bulb/flower, is a rich source of proteins, where the latter parts are often considered as processing discards. The objective of this research was to produce protein hydrolysates from sea cucumber tissues (body wall, flower, and internal organs) with bioactive properties associated with antioxidants, DNA and LDL cholesterol oxidation inhibition, and angiotensin-I-converting enzyme (ACE) inhibitory effects. The protein hydrolysates were prepared using food-grade commercial enzymes, namely Alcalase, Corolase, and Flavourzyme, individually and in combination, and found that the combination of enzymes exhibited stronger antioxidant potential than the individual enzymes, as well as their untreated counterparts. Similar trends were also observed for the DNA and LDL cholesterol oxidation inhibition and ACE-inhibitory properties of sea cucumber protein hydrolysates, mainly those that were prepared from the flower. Thus, the findings of this study revealed potential applications of sea cucumber-derived protein hydrolysates in functional foods, nutraceuticals, and dietary supplements, as well as natural therapeutics.
Topics: Animals; Antioxidants; Angiotensin-Converting Enzyme Inhibitors; Cucumaria; Sea Cucumbers; Protein Hydrolysates; Cholesterol, LDL; Peptidyl-Dipeptidase A
PubMed: 37446924
DOI: 10.3390/molecules28135263 -
International Journal of Molecular... Jul 2023Angiotensin I-converting enzyme (ACE) is an important blood pressure regulator. In this study, we aimed to investigate the ACE-inhibitory effects of meroterpenoids...
Angiotensin I-converting enzyme (ACE) is an important blood pressure regulator. In this study, we aimed to investigate the ACE-inhibitory effects of meroterpenoids isolated from the brown alga, , and the molecular mechanisms underlying ACE inhibition. Four fractions of were prepared using hexane, chloroform, ethyl acetate, and water as solvents and analyzed for their potential ACE-inhibitory effects. The chloroform fraction showed the strongest ACE-inhibitory effect, with an IC value of 0.18 mg/mL. Three meroterpenoids, sargachromenol, 7-methyl sargachromenol, and sargaquinoic acid, were isolated from the chloroform fraction. Meroterpenoids isolated from had IC values of 0.44, 0.37, and 0.14 mM. The molecular docking study revealed that the ACE-inhibitory effect of the isolated meroterpenoids was mainly attributed to Zn-ion, hydrogen bonds, pi-anion, and pi-alkyl interactions between the meroterpenoids and ACE. These results suggest that could be a potential raw material for manufacturing antihypertensive nutraceutical ingredients.
Topics: Angiotensin-Converting Enzyme Inhibitors; Molecular Docking Simulation; Sargassum; Peptidyl-Dipeptidase A; Chloroform
PubMed: 37446242
DOI: 10.3390/ijms241311065 -
The International Journal of... Aug 2023
Corrigendum to: A Study in First-Episode Psychosis Patients: Does Angiotensin I-Converting Enzyme Activity Associated With Genotype Predict Symptom Severity Reductions After Treatment With Atypical Antipsychotic Risperidone?
PubMed: 37433025
DOI: 10.1093/ijnp/pyad038 -
Food Chemistry: X Jun 2023A novel wild-type () L3 with good fermentation characteristics and protein degradation capacity was isolated from raw milk samples. In this study, the metabolites in...
A novel wild-type () L3 with good fermentation characteristics and protein degradation capacity was isolated from raw milk samples. In this study, the metabolites in milk fermented with L3 were investigated by metabolomic and peptidomics analyses. The metabolomics results revealed that the metabolites in milk fermented with L3 were Thr-Pro, Val-Lys, l-creatine, pyridoxine, and muramic acid, which improved the taste and nutritional qualities of the milk. Moreover, the water-soluble peptides derived from L3 fermented milk exhibited high antioxidant properties and angiotensin I-converting enzyme inhibitory (ACEI) activities. Additionally, 152 peptides were found using liquid chromatography-mass spectrometry (LC-MS/MS). Furthermore, endogenous enzymes secreted by L3 cleaved - and -casein to release six ACEI peptides (ACEIPs), nineteen antioxidant peptides (AOPs), and five antimicrobial peptides (AMPS). Overall, these findings could be valuable in improving the quality of fermented milk.
PubMed: 37397209
DOI: 10.1016/j.fochx.2023.100732 -
Chemical & Pharmaceutical Bulletin 2023The root of Rehmannia glutinosa Liboschitz forma hueichingensis HSIAO has been used as a tonic and treatment for urinary and skin disorders in Japanese Kampo medicine....
The root of Rehmannia glutinosa Liboschitz forma hueichingensis HSIAO has been used as a tonic and treatment for urinary and skin disorders in Japanese Kampo medicine. Phytochemical investigation of the root has been well reported, but that of the leaves is limited. To explore the potential value of R. glutinosa leaves, we focused on the angiotensin I-converting enzyme (ACE)-inhibitory activity. The leaf extract exhibited ACE-inhibitory activity, and the inhibitory potency of leaves was stronger than that of roots. Using this activity as an indicator, we isolated linaride (1), 6-O-hydroxybenzoyl ajugol (2), acteoside (3), leucosceptoside A (4), martynoside (5), luteolin (6), apigenin (7), and chrysoeriol (8) by separating and purifying the extract. We then examined the ACE-inhibitory activities of 1-8, catalpol (9), aucubin (10), ajugol (11), and echinacoside (12). Among them, 3, 6, and 12 displayed the most potent inhibitory activity. A simultaneous analytical method was also developed using compounds contained in R. glutinosa leaves and roots, and their contents were compared. The method consisted of extraction with 50% aqueous methanol under sonication for 60 min and LC/MS measurement. R. glutinosa leaves tended to have higher levels of majority of the analytes than the roots, including 3 and 6, which had higher ACE-inhibitory activity. These results suggest that 3 and 6 contribute to the ACE-inhibitory activity of R. glutinosa leaves, which may represent a useful medicinal resource for hypertension.
Topics: Peptidyl-Dipeptidase A; Phytochemicals; Pyrans; Rehmannia
PubMed: 37394599
DOI: 10.1248/cpb.c22-00524 -
Journal of the... 2023Hypertension is a major risk factor for heart attack, produce atherosclerosis (hardening of the arteries), congestive heart failure, stroke, kidney infection, blindness,... (Review)
Review
Angiotensin-Converting Enzyme and Hypertension: A Systemic Analysis of Various ACE Inhibitors, Their Side Effects, and Bioactive Peptides as a Putative Therapy for Hypertension.
Hypertension is a major risk factor for heart attack, produce atherosclerosis (hardening of the arteries), congestive heart failure, stroke, kidney infection, blindness, end-stage renal infection, and cardiovascular diseases. Many mechanisms are involved in causing hypertension, i.e., via calcium channels, alpha and beta receptors, and the renin-angiotensin system (RAS). RAS has an important role in blood pressure control and is also involved in the metabolism of glucose, homeostasis, and balance of electrolytes in the body. The components of RAS that are involved in the regulation of blood pressure are angiotensinogen, Ang I (angiotensin I), Ang II (angiotensin II), ACE (angiotensin-converting enzyme), and ACE 2 (angiotensin-converting enzyme 2). These components provide for relevant therapeutic targets for the treatment of hypertension, and various drugs are commercially available that target individual components of RAS. Angiotensin receptor blockers (ARBs) and ACE inhibitors are the most popular among these drugs. ACE is chosen in this review as it makes an important target for blood pressure control because it converts Ang I into Ang II and also acts on the vasodilator, bradykinin, to degrade it into inactive peptides. This review highlights various aspects of blood pressure regulation in the body with a focus on ACE, drugs targeting the components involved in regulation, their associated side effects, and a need to shift to alternative therapy for putative hypertension treatment in the form of bioactive peptides from food.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Hypertension; Peptides; Angiotensin II
PubMed: 37389408
DOI: 10.1155/2023/7890188