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Journal of Molecular and Cellular... Jan 2020Chronically elevated angiotensin II is a widely-established contributor to hypertension and heart failure via its action on the kidneys and vasculature. It also augments...
Chronically elevated angiotensin II is a widely-established contributor to hypertension and heart failure via its action on the kidneys and vasculature. It also augments the activity of peripheral sympathetic nerves through activation of presynaptic angiotensin II receptors, thus contributing to sympathetic over-activity. Although some cells can synthesise angiotensin II locally, it is not known if this machinery is present in neurons closely coupled to the heart. Using a combination of RNA sequencing and quantitative real-time polymerase chain reaction, we demonstrate evidence for a renin-angiotensin synthesis pathway within human and rat sympathetic stellate ganglia, where significant alterations were observed in the spontaneously hypertensive rat stellate ganglia compared with Wistar stellates. We also used Förster Resonance Energy Transfer to demonstrate that administration of angiotensin II and angiotensin 1-7 peptides significantly elevate cyclic guanosine monophosphate in the rat stellate ganglia. Whether the release of angiotensin peptides from the sympathetic stellate ganglia alters neurotransmission and/or exacerbates cardiac dysfunction in states associated with sympathetic over activity remains to be established.
Topics: Adult; Aged; Angiotensins; Animals; Cyclic GMP; Female; Gene Expression Regulation; Humans; Male; Middle Aged; Models, Biological; Nucleotides, Cyclic; Principal Component Analysis; RNA, Messenger; Rats, Inbred SHR; Rats, Wistar; Renin; Stellate Ganglion; Sympathetic Nervous System; Transcriptome; Young Adult
PubMed: 31836539
DOI: 10.1016/j.yjmcc.2019.11.157 -
Scientific Reports Mar 2021This study aimed to focus on the high-value utilization of raw wheat gluten by determining the potent antioxidant peptides and angiotensin I-converting enzyme (ACE)...
This study aimed to focus on the high-value utilization of raw wheat gluten by determining the potent antioxidant peptides and angiotensin I-converting enzyme (ACE) inhibitory peptides from wheat gluten oligopeptides (WOP). WOP were analyzed for in vitro antioxidant activity and inhibition of ACE, and the identification of active peptides was performed by reversed-phase high-performance liquid chromatography and mass spectrometry. Quantitative analysis was performed for highly active peptides. Five potent antioxidant peptides, Leu-Tyr, Pro-Tyr, Tyr-Gln, Ala-Pro-Ser-Tyr and Arg-Gly-Gly-Tyr (6.07 ± 0.38, 7.28 ± 0.29, 11.18 ± 1.02, 5.93 ± 0.20 and 9.04 ± 0.47 mmol 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) equivalent/g sample, respectively), and five potent ACE inhibitory peptides, Leu-Tyr, Leu-Val-Ser, Tyr-Gln, Ala-Pro-Ser-Tyr and Arg-Gly-Gly-Tyr (half maximal inhibitory concentration (IC) values = 0.31 ± 0.02, 0.60 ± 0.03, 2.00 ± 0.13, 1.47 ± 0.08 and 1.48 ± 0.11 mmol/L, respectively), were observed. The contents of Leu-Tyr, Pro-Tyr, Tyr-Gln, Ala-Pro-Ser-Tyr, Arg-Gly-Gly-Tyr, and Leu-Val-Ser were 155.04 ± 8.36, 2.08 ± 0.12, 1.95 ± 0.06, 22.70 ± 1.35, 0.25 ± 0.01, and 53.01 ± 2.73 μg/g, respectively, in the WOP. Pro-Tyr, Tyr-Gln, Ala-Pro-Ser-Tyr, Arg-Gly-Gly-Tyr, and Leu-Val-Ser are novel antioxidative/ACE inhibitory peptides that have not been previously reported. The results suggest that WOP could potentially be applied in the food industry as a functional additive.
Topics: Amino Acid Sequence; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Antioxidants; Glutens; Mass Spectrometry; Peptide Fragments; Peptides; Peptidyl-Dipeptidase A; Triticum
PubMed: 33664447
DOI: 10.1038/s41598-021-84820-7 -
Clinical Science (London, England :... Mar 2020Adverse events during fetal life such as insufficient protein intake or elevated transfer of glucocorticoid to the fetus may impact cardiovascular and metabolic health... (Review)
Review
Adverse events during fetal life such as insufficient protein intake or elevated transfer of glucocorticoid to the fetus may impact cardiovascular and metabolic health later in adult life and are associated with increased incidence of type 2 diabetes, ischemic heart disease and hypertension. Several adverse factors converge and suppress the fetal renin-angiotensin-aldosterone system (RAAS). The aim of this review is to summarize data on the significance of RAAS for kidney development and adult hypertension. Genetic inactivation of RAAS in rodents at any step from angiotensinogen to angiotensin II (ANGII) type 1 receptor (AT1) receptors or pharmacologic inhibition leads to complex developmental injury to the kidneys that has also been observed in human case reports. Deletion of the 'protective' arm of RAAS, angiotensin converting enzyme (ACE) 2 (ACE-2) and G-protein coupled receptor for Angiotensin 1-7 (Mas) receptor does not reproduce the AT1 phenotype. The changes comprise fewer glomeruli, thinner cortex, dilated tubules, thicker arterioles and arteries, lack of vascular bundles, papillary atrophy, shorter capillary length and volume in cortex and medulla. Altered activity of systemic and local regulators of fetal-perinatal RAAS such as vitamin D and cyclooxygenase (COX)/prostaglandins are associated with similar injuries. ANGII-AT1 interaction drives podocyte and epithelial cell formation of vascular growth factors, notably vascular endothelial growth factor (VEGF) and angiopoietins (Angpts), which support late stages of glomerular and cortical capillary growth and medullary vascular bundle formation and patterning. RAAS-induced injury is associated with lower glomerular filtration rate (GFR), lower renal plasma flow, kidney fibrosis, up-regulation of sodium transporters, impaired sodium excretion and salt-sensitive hypertension. The renal component and salt sensitivity of programmed hypertension may impact dietary counseling and choice of pharmacological intervention to treat hypertension.
Topics: Angiotensins; Animals; Blood Pressure; Humans; Hypertension; Kidney; Renin; Renin-Angiotensin System; Vascular Endothelial Growth Factor A
PubMed: 32219345
DOI: 10.1042/CS20190765 -
Advances in Pharmacology (San Diego,... 2023Renin-angiotensin system (RAS) plays an indispensable role in regulating blood pressure through its effects on fluid and electrolyte balance. As an aside, cumulative...
Renin-angiotensin system (RAS) plays an indispensable role in regulating blood pressure through its effects on fluid and electrolyte balance. As an aside, cumulative evidence from experimental to clinical studies supports the notion that dysregulation of RAS contributes to the pro-inflammatory, pro-oxidative, and pro-fibrotic processes that occur in pulmonary diseases like asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and acute lung injury (ALI). Pharmacological intervention of the various RAS components can be a novel therapeutic strategy for the treatment of these respiratory diseases. In this chapter, we first give a recent update on the RAS, and then compile, review, and analyse recent reports on targeting RAS components as treatments for respiratory diseases. Inhibition of the pro-inflammatory renin, angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and Ang II type 1 receptor (AT1R) axis, and activation of the protective ACE2, AT2R, Ang (1-7), and Mas receptor axis have demonstrated varying degrees of efficacies in experimental respiratory disease models or in human trials. The newly identified alamandine/Mas-related G-protein-coupled receptor member D pathway has shown some therapeutic promise as well. However, our understanding of the RAS ligand-and-receptor interactions is still inconclusive, and the modes of action and signaling cascade mediating the newly identified RAS receptors remain to be better characterized. Clinical data are obviously lacking behind the promising pre-clinical findings of certain well-established molecules targeting at different pathways of the RAS in respiratory diseases. Translational human studies should be the focus for RAS drug development in lung diseases in the next decade.
Topics: Humans; Renin-Angiotensin System; Signal Transduction; Fibrosis; Respiratory Tract Diseases; Angiotensins; Angiotensin II; Angiotensin I; Peptide Fragments; Receptor, Angiotensin, Type 1
PubMed: 37524485
DOI: 10.1016/bs.apha.2023.02.002 -
Molecules (Basel, Switzerland) Mar 2022The binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein to its cellular receptor, the angiotensin-converting enzyme 2 (ACE2),... (Review)
Review
The binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein to its cellular receptor, the angiotensin-converting enzyme 2 (ACE2), causes its downregulation, which subsequently leads to the dysregulation of the renin-angiotensin system (RAS) in favor of the ACE-angiotensin II (Ang II)-angiotensin II type I receptor (AT1R) axis. AT1R has a major role in RAS by being involved in several physiological events including blood pressure control and electrolyte balance. Following SARS-CoV-2 infection, pathogenic episodes generated by the vasoconstriction, proinflammatory, profibrotic, and prooxidative consequences of the Ang II-AT1R axis activation are accompanied by a hyperinflammatory state (cytokine storm) and an acute respiratory distress syndrome (ARDS). AT1R, a member of the G protein-coupled receptor (GPCR) family, modulates Ang II deleterious effects through the activation of multiple downstream signaling pathways, among which are MAP kinases (ERK 1/2, JNK, p38MAPK), receptor tyrosine kinases (PDGF, EGFR, insulin receptor), and nonreceptor tyrosine kinases (Src, JAK/STAT, focal adhesion kinase (FAK)), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. COVID-19 is well known for generating respiratory symptoms, but because ACE2 is expressed in various body tissues, several extrapulmonary pathologies are also manifested, including neurologic disorders, vasculature and myocardial complications, kidney injury, gastrointestinal symptoms, hepatic injury, hyperglycemia, and dermatologic complications. Therefore, the development of drugs based on RAS blockers, such as angiotensin II receptor blockers (ARBs), that inhibit the damaging axis of the RAS cascade may become one of the most promising approaches for the treatment of COVID-19 in the near future. We herein review the general features of AT1R, with a special focus on the receptor-mediated activation of the different downstream signaling pathways leading to specific cellular responses. In addition, we provide the latest insights into the roles of AT1R in COVID-19 outcomes in different systems of the human body, as well as the role of ARBs as tentative pharmacological agents to treat COVID-19.
Topics: Angiotensin I; Angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Humans; Receptor, Angiotensin, Type 1; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35408447
DOI: 10.3390/molecules27072048 -
Archives of Physiology and Biochemistry Oct 2022The renin-angiotensin system (RAS), which is important for controlling haemostasis in the body, can increase the development of essential hypertension (HTN). Various...
The renin-angiotensin system (RAS), which is important for controlling haemostasis in the body, can increase the development of essential hypertension (HTN). Various surveys have shown that ACE I/D polymorphism that influences ACE activity, a key component of RAS, has been known to be associated with the risk of HTN. The goal of this study was to investigate the correlation between ACE (I/D) polymorphism and HTN. Blood samples were obtained from 102 patients and 104 healthy individuals. The two groups were matched by age and sex. Informed consent was prepared for the study. The demographic data were collected using a questionnaire. White blood cells (WBCs) and then DNA were extracted from whole blood. After this, the PCR test was performed using specific primers. PCR products were examined using 1% agarose gel. Individuals with genotype II having a band of 490 bp, ID two band of 490 bp and 190 bp, and individuals with DD genotype, have a band in region 190 bp. The average age of the patients was 52.7 ± 7.5 years. A significant difference was seen in the distribution of DD, II and I/D genotypes of ACE polymorphism between the essential hypertensive patients (44.1, 10.8, and 45.1%) and their ethnically matched healthy control (61.5, 3.8, and 24.6%, respectively). Our study showed an increased risk of disease in people with II genotype in comparison to ID and DD genotypes (0.46 (0.1-1.75) and 0.26 (0.05-0.94), respectively). The present study demonstrated that ACEI/D polymorphism is characterised with greater risk of essential HTN in the Lorestan province. II genotype increased the relative risk of essential HTN in the population. In the future, more investigations with more samples size are recommended for the better study of genetic factors in hypertensive patients.
Topics: Angiotensins; DNA; Genotype; Humans; Hypertension; Middle Aged; Mutagenesis, Insertional; Peptidyl-Dipeptidase A; Sepharose
PubMed: 32401071
DOI: 10.1080/13813455.2020.1762225 -
Biomarkers : Biochemical Indicators of... Mar 2023The persistent and alarming rates of increase in cardiovascular and renal diseases caused by chemicals such as cobalt chloride (CoCl) in mammalian tissues have led to...
The persistent and alarming rates of increase in cardiovascular and renal diseases caused by chemicals such as cobalt chloride (CoCl) in mammalian tissues have led to the use of various drugs for the treatment of these diseases. This study aims at evaluating the nephron-protective action of Naringin (NAR), a metal-chelating antioxidant against CoCl-induced hypertension and nephrotoxicity.Forty-two male Wistar rats were randomly distributed to seven rats of six groups and classified into Group A (Control), Group B (300 part per million; ppm CoCl), Group C (300 ppm CoCl + 80 mg/kg NAR), Group D (300 ppm CoCl + 160 mg/kg NAR), Group E (80 mg/kg NAR), and Group F (160 mg/kg NAR). NAR and CoCl were administered via oral gavage for seven days. Biomarkers of renal damage, oxidative stress, antioxidant status, blood pressure parameters, immunohistochemistry of renal angiotensin-converting enzyme and podocin were determined.Cobalt chloride intoxication precipitated hypertension, renal damage, and oxidative stress. Immunohistochemistry revealed higher expression of angiotensin-converting enzyme (ACE) and podocin in rats administered only CoCl.Taken together, the antioxidant and metal-chelating action of Naringin administration against cobalt chloride-induced renal damage and hypertension could be through abrogation of angiotensin-converting enzyme and podocin signalling pathway.
Topics: Rats; Male; Animals; Antioxidants; Rats, Wistar; Cobalt; Hypertension; Drug-Related Side Effects and Adverse Reactions; Angiotensins; Mammals
PubMed: 36480283
DOI: 10.1080/1354750X.2022.2157489 -
Molecular and Cellular Endocrinology Jun 2021The identification of an alternate extended form of angiotensin I composed of the first twelve amino acids at the N-terminal of angiotensinogen has generated new... (Review)
Review
The identification of an alternate extended form of angiotensin I composed of the first twelve amino acids at the N-terminal of angiotensinogen has generated new knowledge of the importance of noncanonical mechanisms for renin independent generation of angiotensins. The human sequence of the dodecapeptide angiotensin-(1-12) [N-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Va-Ile-COOH] is an endogenous substrate that in the rat has been documented to be present in multiple organs including the heart, brain, kidney, gut, adrenal gland, and the bone marrow. Newer studies have confirmed the existence of Ang-(1-12) as an Ang II-forming substrate in the blood and heart of normal and diseased patients. Studies to-date document that angiotensin II generation from angiotensin-(1-12) does not require renin participation while chymase rather than angiotensin converting enzyme shows high catalytic activity in converting this tissue substrate into angiotensin II directly.
Topics: Adrenal Glands; Angiotensin I; Angiotensin II; Angiotensinogen; Animals; Biocatalysis; Bone Marrow; Brain; Cardiovascular Diseases; Chymases; Gene Expression; Humans; Intestines; Kidney; Myocardium; Peptide Fragments; Rats; Renin-Angiotensin System
PubMed: 33309638
DOI: 10.1016/j.mce.2020.111119 -
The Journal of Small Animal Practice May 2022To determine the efficacy and adverse events of the administration of angiotensin--converting enzyme inhibitors for the management of preclinical myxomatous mitral valve... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To determine the efficacy and adverse events of the administration of angiotensin--converting enzyme inhibitors for the management of preclinical myxomatous mitral valve disease in dogs.
MATERIALS AND METHODS
A compre- hensive search using Pubmed/MEDLINE, LILACS and CAB abstracts databases was performed. Ran- domised clinical trials that assessed efficacy and adverse events of angiotensin-converting enzyme inhibitors for the management of preclinical myxomatous mitral valve disease in dogs were included. Certainty of evidence was rated using GRADE methods.
RESULTS
Four randomised clinical trials were included. While safe, angiotensin-converting enzyme inhibitors administration to dogs with myxomatous mitral valve disease and cardiomegaly results in little to no difference in the risk of development congestive heart failure (high certainty of evidence; relative risk: 1.03; 95% confidence interval: 0.87 to 1.23) and may result in little to no difference in cardiovascular-related (low certainty of evidence; relative risk: 1.01; 95% confidence interval: 0.54 to 1.89) and all-cause mortality (low certainty of evidence; relative risk: 0.93; 95% confidence interval: 0.63 to 1.36). Administration of angiotensin-converting enzyme inhibitors to dogs with myxomatous mitral valve disease without cardiomegaly may result in a reduced risk of congestive heart failure development. However, the range in which the actual effect for this outcome may be, the "margin of error," indicates it might also increase the risk of congestive heart failure development (low certainty of evidence; relative risk: 0.86; 95% confidence interval: 0.54 to 1.35).
CLINICAL SIGNIFICANCE
Administration of angiotensin-converting enzyme inhibitors to dogs with -preclinical myxoma- tous mitral valve disease and cardiomegaly results in little to no difference in the risk of the develop- ment of congestive heart failure and may result in little to no difference in -cardiovascular-related and all-cause mortality. The certainty of evidence of the efficacy of angiotensin-converting enzyme inhibi- tors administration to dogs without cardiomegaly was low.
Topics: Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Animals; Cardiomegaly; Dog Diseases; Dogs; Heart Failure; Mitral Valve
PubMed: 34905219
DOI: 10.1111/jsap.13461 -
Inflammation Research : Official... Dec 2022The current study aimed to summarize the evidence of compounds contained in plant species with the ability to block the angiotensin-converting enzyme 2 (ACE-II), through... (Review)
Review
OBJECTIVE AND DESIGN
The current study aimed to summarize the evidence of compounds contained in plant species with the ability to block the angiotensin-converting enzyme 2 (ACE-II), through a scoping review.
METHODS
PubMed and Scopus electronic databases were used for the systematic search and a manual search was performed RESULTS: Studies included were characterized as in silico. Among the 200 studies retrieved, 139 studies listed after the exclusion of duplicates and 74 were included for the full read. Among them, 32 studies were considered eligible for the qualitative synthesis. The most evaluated class of secondary metabolites was flavonoids with quercetin and curcumin as most actives substances and terpenes (isothymol, limonin, curcumenol, anabsinthin, and artemisinin). Other classes that were also evaluated were alkaloid, saponin, quinone, substances found in essential oils, and primary metabolites as the aminoacid L-tyrosine and the lipidic compound 2-monolinolenin.
CONCLUSION
This review suggests the most active substance from each class of metabolites, which presented the strongest affinity to the ACE-II receptor, what contributes as a basis for choosing compounds and directing the further experimental and clinical investigation on the applications these compounds in biotechnological and health processes as in COVID-19 pandemic.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Pandemics; Flavonoids; Angiotensins; COVID-19 Drug Treatment
PubMed: 36307652
DOI: 10.1007/s00011-022-01642-7