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Journal of Physiology and Pharmacology... Apr 2024We have previously described local aldosterone synthesis in mouse colon. In the renin-angiotensin-aldosterone system (RAAS), angiotensin II (Ang II) peptide is the...
We have previously described local aldosterone synthesis in mouse colon. In the renin-angiotensin-aldosterone system (RAAS), angiotensin II (Ang II) peptide is the physiological factor which stimulates aldosterone synthesis in the adrenal glands. We have recently demonstrated that Ang II stimulates aldosterone synthesis also in mouse colon. Here, we conducted a 75-min ex vivo incubation of murine colonic tissue and evaluated the effects of three other Ang peptides, Ang I (1 μM), Ang III (0.1 μM) and Ang (1-7) (0.1 μM) on aldosterone synthesis. As a possible mechanism, their effects on tissue levels of the rate-limiting enzyme, aldosterone synthase (CYP11B2) were measured by ELISA and Western blot. Ang III significantly elevated the amount of tissue CYP11B2 protein in colon. The values of released aldosterone in colon tissue incubation were increased over the control in the presence of Ang I, II or III, however, being statistically non-significant. In Western blot analysis, the values of tissue CYP11B2 protein content were elevated by Ang I and II. Ang (1-7) alone in colon did not influence CYP11B2 protein levels in the incubation experiment but showed higher aldosterone release without statistical significance. Ang (1-7) showed an antagonistic effect towards Ang II in release of aldosterone in adrenal gland. An overall estimation of a single peptide (three measured variables), the results were always in an increasing direction. The responses of aldosterone synthesis to high levels of glucose (44 mM) and potassium (18.8 mM) as physiological stimulators in vivo were investigated in the colon incubation. Glucose, equal to four times the concentration of the control buffer in the incubation, showed higher values of aldosterone release in colon than control without statistical significance similarly to the effect seen in adrenal glands. Increasing the concentration of potassium in the incubation buffer exerted no effect on colonic aldosterone production. Intriguingly, no correlation was found between aldosterone release and the tissue CYP11B2 protein content in colon. In summary, the response of colonic aldosterone synthesis to different Ang peptides resembles, but is not identical to, the situation in the adrenal glands.
Topics: Animals; Male; Mice; Aldosterone; Angiotensin I; Angiotensin II; Angiotensin III; Colon; Cytochrome P-450 CYP11B2; Glucose; Peptide Fragments; Potassium
PubMed: 38736265
DOI: 10.26402/jpp.2024.2.07 -
PloS One 2024The Ang-(1-7)/MasR axis is critically involved in treating several diseases; For example, Ang-(1-7) improves inflammatory response and neurological function after...
The Ang-(1-7)/MasR axis is critically involved in treating several diseases; For example, Ang-(1-7) improves inflammatory response and neurological function after traumatic brain injury and inhibits post-inflammatory hypothermia. However, its function in traumatic brain injury (TBI) combined with seawater immersion hypothermia remains unclear. Here, we used a mice model of hypothermic TBI and a BV2 cell model of hypothermic inflammation to investigate whether the Ang-(1-7)/MasR axis is involved in ameliorating hypothermic TBI. Quantitative reverse transcription PCR, western blotting assay, and immunofluorescence assay were performed to confirm microglia polarization and cytokine regulation. Hematoxylin-eosin staining, Nissl staining, and immunohistochemical assay were conducted to assess the extent of hypothermic TBI-induced damage and the ameliorative effect of Ang-(1-7) in mice. An open field experiment and neurological function scoring with two approaches were used to assess the degree of recovery and prognosis in mice. After hypothermic TBI establishment in BV2 cells, the Ang-(1-7)/MasR axis induced phenotypic transformation of microglia from M1 to M2, inhibited IL-6 and IL-1β release, and upregulated IL-4 and IL-10 levels. After hypothermic TBI development in mice, intraperitoneally administered Ang-(1-7) attenuated histological damage and promoted neurological recovery. These findings suggest that hypothermia exacerbates TBI-induced damage and that the Ang-(1-7)/MasR axis can ameliorate hypothermic TBI and directly affect prognosis.
Topics: Animals; Microglia; Brain Injuries, Traumatic; Mice; Peptide Fragments; Angiotensin I; Male; Neuroinflammatory Diseases; Mice, Inbred C57BL; Receptors, G-Protein-Coupled; Phenotype; Disease Models, Animal; Hypothermia, Induced; Cytokines; Cell Line; Hypothermia; Inflammation
PubMed: 38728304
DOI: 10.1371/journal.pone.0303150 -
Cytokine Jul 2024Sepsis is understood as the result of initiating systemic inflammation derived from an inadequate host response against pathogens. In its acute phase, sepsis is marked...
Sepsis is understood as the result of initiating systemic inflammation derived from an inadequate host response against pathogens. In its acute phase, sepsis is marked by an exacerbated reaction to infection, tissue damage, organ failure, and metabolic dysfunction. Among these, hypoglycemia, characterized by disorders of the gluconeogenesis pathway, is related to one of the leading causes of mortality in septic patients. Recent research has investigated the involvement of sympathetic efferent neuroimmune pathways during systemic inflammation. These pathways can be stimulated by several centrally administered drugs, including Angiotensin-(1-7) (Ang-(1-7)). Therefore, the present study aims to evaluate the effects of central treatment with Ang-(1-7) on hypoglycemia during endotoxemia. For this, male Wistar Hannover rats underwent stereotaxic surgery for intracerebroventricular (i.c.v.) administration of Ang-(1-7) and cannulation of the jugular vein for lipopolysaccharide (LPS) injection. Our results demonstrate that LPS was capable of inducing hypoglycemia and that prior central treatment with Ang-(1-7) attenuated this effect. Our data also show that Ang-(1-7) reduced plasma concentrations of TNF-α, IL-1β, IL-6, and nitric oxide, in addition to the decrease and increase of hepatic IL-6 and IL-10 respectively, in animals subjected to systemic inflammation by LPS, resulting in the reduction of systemic and hepatic inflammation, thus attenuating the deleterious effects of LPS on phosphoenolpyruvate carboxykinase protein content. In summary, the data suggest that central treatment with Ang-(1-7) attenuates hypoglycemia induced by endotoxemia, probably through anti-inflammatory action, leading to reestablishing hepatic gluconeogenesis.
Topics: Animals; Angiotensin I; Male; Sepsis; Peptide Fragments; Rats, Wistar; Hypoglycemia; Rats; Lipopolysaccharides; Inflammation; Liver; Nitric Oxide; Hepatitis; Endotoxemia; Cytokines; Gluconeogenesis; Blood Glucose; Tumor Necrosis Factor-alpha
PubMed: 38723454
DOI: 10.1016/j.cyto.2024.156637 -
Biochemical Pharmacology Jun 2024Delayed neurocognitive recovery (dNCR) is a common complication in geriatric surgical patients. The impact of anesthesia and surgery on patients with neurodegenerative...
Delayed neurocognitive recovery (dNCR) is a common complication in geriatric surgical patients. The impact of anesthesia and surgery on patients with neurodegenerative diseases, such as Parkinson's disease (PD) or prion disease, has not yet been reported. In this study, we aimed to determine the association between a pre-existing A53T genetic background, which involves a PD-related point mutation, and the development of postoperative dNCR. We observed that partial hepatectomy induced hippocampus-dependent cognitive deficits in 5-month-old A53T transgenic mice, a model of early-stage PD without cognitive deficits, unlike in age-matched wild-type (WT) mice. We respectively examined molecular changes at 6 h, 1 day, and 2 days after partial hepatectomy and observed that cognitive changes were accompanied by weakened angiotensin-(1-7)/Mas receptor [Ang-(1-7)/MasR] axis, increased alpha-synuclein (α-syn) expression and phosphorylation, decreased methylated protein phosphatase-2A (Me-PP2A), and prompted microglia M1 polarization and neuronal apoptosis in the hippocampus at 1 day after surgery. Nevertheless, no changes in blood-brain barrier (BBB) integrity or plasma α-syn levels in either A53T or WT mice. Furthermore, intranasal administration of selective MasR agonist AVE 0991, reversed the mentioned cognitive deficits in A53T mice, enhanced MasR expression, reduced α-syn accumulation and phosphorylation, and attenuated microglia activation and apoptotic response. Our findings suggest that individuals with the A53T genetic background may be more susceptible to developing postoperative dNCR. This susceptibility could be linked to central α-syn accumulation mediated by the weakened Ang-(1-7)/MasR/methyl-PP2A signaling pathway in the hippocampus following surgery, independent of plasma α-syn level and BBB.
Topics: Animals; Humans; Male; Mice; alpha-Synuclein; Angiotensin I; Hippocampus; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Peptide Fragments; Postoperative Cognitive Complications; Postoperative Complications; Proto-Oncogene Mas; Proto-Oncogene Proteins; Receptors, G-Protein-Coupled
PubMed: 38705534
DOI: 10.1016/j.bcp.2024.116261 -
Journal of Hypertension Jun 2024Isolated nocturnal hypertension (INHT), defined as nighttime elevated blood pressure (BP) with normal daytime BP assessed by ambulatory BP monitoring, is associated with...
Isolated nocturnal hypertension (INHT), defined as nighttime elevated blood pressure (BP) with normal daytime BP assessed by ambulatory BP monitoring, is associated with higher cardiovascular morbidity and mortality. We hypothesized that an alteration in the circulating renin-angiotensin system (RAS) contributes to INHT development. We examined circulating levels of angiotensin (Ang) (1-7) and Ang II and ACE2 activity in 26 patients that met the INHT criteria, out of 50 that were referred for BP evaluation (62% women, 45 ± 16 years old). Those with INHT were older, had a higher BMI, lower circulating Ang-(1-7) (P = 0.002) and Ang II levels (P = 0.02) and no change in ACE2 activity compared to those normotensives. Nighttime DBP was significantly correlated with Ang-(1-7) and Ang II levels. Logistic regression showed significant association in Ang-(1-7) and Ang II levels with INHT. Our study reveals differences in circulating RAS in individuals with INHT.
Topics: Humans; Angiotensin I; Female; Male; Middle Aged; Peptide Fragments; Hypertension; Adult; Angiotensin II; Renin-Angiotensin System; Circadian Rhythm; Blood Pressure; Angiotensin-Converting Enzyme 2; Blood Pressure Monitoring, Ambulatory; Peptidyl-Dipeptidase A
PubMed: 38690908
DOI: 10.1097/HJH.0000000000003728 -
World Journal of Diabetes Apr 2024Coronavirus disease 2019 (COVID-19) is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus. It... (Review)
Review
Coronavirus disease 2019 (COVID-19) is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus. It has affected over 768 million people worldwide, resulting in approximately 6900000 deaths. High-risk groups, identified by the Centers for Disease Control and Prevention, include individuals with conditions like type 2 diabetes mellitus (T2DM), obesity, chronic lung disease, serious heart conditions, and chronic kidney disease. Research indicates that those with T2DM face a heightened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals. Examining the renin-angiotensin system (RAS), a vital regulator of blood pressure and pulmonary stability, reveals the significance of the angiotensin-converting enzyme (ACE) and ACE2 enzymes. ACE converts angiotensin-I to the vasoconstrictor angiotensin-II, while ACE2 counters this by converting angiotensin-II to angiotensin 1-7, a vasodilator. Reduced ACE2 expression, common in diabetes, intensifies RAS activity, contributing to conditions like inflammation and fibrosis. Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels, concerns arise regarding the potential elevation of ACE2 receptors on cell membranes, potentially facilitating COVID-19 entry. This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome coronavirus 2 infection and associated complications in T2DM. Potential treatment strategies, including recombinant human ACE2 therapy, broad-spectrum antiviral drugs, and epigenetic signature detection, are discussed as promising avenues in the battle against this pandemic.
PubMed: 38680697
DOI: 10.4239/wjd.v15.i4.606 -
Inflammation Research : Official... Jun 2024Angiotensin-(1-7) [Ang-(1-7)] is a pro-resolving mediator. It is not known whether the pro-resolving effects of Ang-(1-7) are sustained and protect the lung from a...
OBJECTIVE
Angiotensin-(1-7) [Ang-(1-7)] is a pro-resolving mediator. It is not known whether the pro-resolving effects of Ang-(1-7) are sustained and protect the lung from a subsequent inflammatory challenge. This study sought to investigate the impact of treatment in face of a second allergic or lipopolysaccharide (LPS) challenge.
METHODS
Mice, sensitized and challenged with ovalbumin (OVA), received a single Ang-(1-7) dose at the peak of eosinophilic inflammation, 24 h after the final OVA challenge. Subsequently, mice were euthanized at 48, 72, 96, and 120 h following the OVA challenge, and cellular infiltrate, inflammatory mediators, lung histopathology, and macrophage-mediated efferocytic activity were evaluated. The secondary inflammatory stimulus (OVA or LPS) was administered 120 h after the last OVA challenge, and subsequent inflammatory analyses were performed.
RESULTS
Treatment with Ang-(1-7) resulted in elevated levels of IL-10, CD4Foxp3, Mres in the lungs and enhanced macrophage-mediated efferocytic capacity. Moreover, in allergic mice treated with Ang-(1-7) and then subjected to a secondary OVA challenge, inflammation was also reduced. Similarly, in mice exposed to LPS, Ang-(1-7) effectively prevented the lung inflammation.
CONCLUSION
A single dose of Ang-(1-7) resolves lung inflammation and protect the lung from a subsequent inflammatory challenge highlighting its potential therapeutic for individuals with asthma.
Topics: Animals; Angiotensin I; Peptide Fragments; Lung; Lipopolysaccharides; Ovalbumin; Mice; Male; Macrophages; Eosinophils; Mice, Inbred BALB C; Inflammation; Eosinophilia; Bronchoalveolar Lavage Fluid
PubMed: 38656426
DOI: 10.1007/s00011-024-01880-x -
Critical Care (London, England) Apr 2024Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARB) medications are widely prescribed. We sought to assess how pre-admission use of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARB) medications are widely prescribed. We sought to assess how pre-admission use of these medications might impact the response to angiotensin-II treatment during vasodilatory shock.
METHODS
In a post-hoc subgroup analysis of the randomized, placebo-controlled, Angiotensin Therapy for High Output Shock (ATHOS-3) trial, we compared patients with chronic angiotensin-converting enzyme inhibitor (ACEi) use, and patients with angiotensin receptor blocker (ARB) use, to patients without exposure to either ACEi or ARB. The primary outcome was mean arterial pressure after 1-h of treatment. Additional clinical outcomes included mean arterial pressure and norepinephrine equivalent dose requirements over time, and study-drug dose over time. Biological outcomes included baseline RAS biomarkers (renin, angiotensin-I, angiotensin-II, and angiotensin-I/angiotensin-II ratio), and the change in renin from 0 to 3 h.
RESULTS
We included n = 321 patients, of whom, 270 were ACEi and ARB-unexposed, 29 were ACEi-exposed and 22 ARB-exposed. In ACEi/ARB-unexposed patients, angiotensin-treated patients, compared to placebo, had higher hour-1 mean arterial pressure (9.1 mmHg [95% CI 7.6-10.1], p < 0.0001), lower norepinephrine equivalent dose over 48-h (p = 0.0037), and lower study-drug dose over 48-h (p < 0.0001). ACEi-exposed patients treated with angiotensin-II showed similarly higher hour-1 mean arterial pressure compared to ACEi/ARB-unexposed (difference in treatment-effect: - 2.2 mmHg [95% CI - 7.0-2.6], p = 0.38), but a greater reduction in norepinephrine equivalent dose (p = 0.0031) and study-drug dose (p < 0.0001) over 48-h. In contrast, ARB-exposed patients showed an attenuated effect of angiotensin-II on hour-1 mean arterial pressure versus ACEi/ARB-unexposed (difference in treatment-effect: - 6.0 mmHg [95% CI - 11.5 to - 0.6], p = 0.0299), norepinephrine equivalent dose (p < 0.0001), and study-drug dose (p = 0.0008). Baseline renin levels and angiotensin-I/angiotensin-II ratios were highest in ACEi-exposed patients. Finally, angiotensin-II treatment reduced hour-3 renin in ACEi/ARB-unexposed and ACEi-exposed patients but not in ARB-exposed patients.
CONCLUSIONS
In vasodilatory shock patients, the cardiovascular and biological RAS response to angiotensin-II differed based upon prior exposure to ACEi and ARB medications. ACEi-exposure was associated with increased angiotensin II responsiveness, whereas ARB-exposure was associated with decreased responsiveness. These findings have clinical implications for patient selection and dosage of angiotensin II in vasodilatory shock. Trial Registration ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Angiotensin II; Renin; Angiotensin Receptor Antagonists; Shock; Norepinephrine
PubMed: 38637829
DOI: 10.1186/s13054-024-04910-6 -
Journal of the American Society For... May 2024This work discusses the effectiveness of the previously developed comprehensive calculation model to optimize linear MALDI-TOF mass spectrometers. The model couples...
This work discusses the effectiveness of the previously developed comprehensive calculation model to optimize linear MALDI-TOF mass spectrometers. The model couples space- and velocity-focusing to precisely analyze the flight-time distribution of ions and predict optimal experimental parameters for the highest mass resolving power. Experimental validation was conducted using a laboratory-made instrument to analyze CsI and angiotensin I ions in low to medium / range. The results indicate that the predicted optimal extraction voltage and delay were reasonably accurate and effective. In the low / range, the peak width obtained using optimal parameters reached the sub nanosecond range, corresponding to a mass resolving power of 10 000-17 000, or 20 000-34 000 if shot-to-shot random fluctuations were minimized by the dynamic data correction method. The observed optimal mass resolving power in the current experiment is 4.8-7.8 times that of commercial instruments. Practical limitations resulting in the gap between the observed and theoretical ultimate mass resolving power are discussed.
PubMed: 38634762
DOI: 10.1021/jasms.4c00018 -
Probiotics and Antimicrobial Proteins Apr 2024Due to its alleged health advantages, several uses in biotechnology and food safety, the well-known probiotic strain Lactiplantibacillus plantarum K25 has drawn...
Genotypic Profiling, Functional Analysis, Cholesterol-Lowering Ability, and Angiotensin I-Converting Enzyme (ACE) Inhibitory Activity of Probiotic Lactiplantibacillus plantarum K25 via Different Approaches.
Due to its alleged health advantages, several uses in biotechnology and food safety, the well-known probiotic strain Lactiplantibacillus plantarum K25 has drawn interest. This in-depth investigation explores the genetic diversity, makeup, and security characteristics of the microbial genome of L. plantarum K25, providing insightful knowledge about its genotypic profile and functional characteristics. Utilizing cutting-edge bioinformatics techniques like comparative genomics, pan-genomics, and genotypic profiling was carried out to reveal the strain's multidimensional potential in various fields. The results not only add to our understanding of the genetic makeup of L. plantarum K25 but also show off its acceptability in various fields, notably in biotechnology and food safety. The explanation of evolutionary links, which highlights L. plantarum K25's aptitude as a probiotic, is one notable finding from this research. Its safety profile, which is emphasized by the absence of genes linked to antibiotic resistance, is crucial and supports its status as a promising probiotic option.
PubMed: 38613617
DOI: 10.1007/s12602-024-10258-8