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1.
Antioxidants (Basel) ; 13(6)2024 Jun 04.
Article de Anglais | MEDLINE | ID: mdl-38929130

RÉSUMÉ

Cardiovascular diseases (CVDs) are often associated with impaired nitric oxide (NO) bioavailability, a critical pathophysiological alteration in CVDs and an important target for therapeutic interventions. Recent studies have revealed the potential of inorganic nitrite and nitrate as sources of NO, offering promising alternatives for managing various cardiovascular conditions. It is now becoming clear that taking advantage of enzymatic pathways involved in nitrite reduction to NO is very relevant in new therapeutics. However, recent studies have shown that nitrite may be bioactivated in the acidic gastric environment, where nitrite generates NO and a variety of S-nitrosating compounds that result in increased circulating S-nitrosothiol concentrations and S-nitrosation of tissue pharmacological targets. Moreover, transnitrosation reactions may further nitrosate other targets, resulting in improved cardiovascular function in patients with CVDs. In this review, we comprehensively address the mechanisms and relevant effects of nitrate and nitrite-stimulated gastric S-nitrosothiol formation that may promote S-nitrosation of pharmacological targets in various CVDs. Recently identified interfering factors that may inhibit these mechanisms and prevent the beneficial responses to nitrate and nitrite therapy were also taken into consideration.

2.
Nutrients ; 16(10)2024 May 14.
Article de Anglais | MEDLINE | ID: mdl-38794713

RÉSUMÉ

Hypertensive diseases of pregnancy (HDPs) represent a global clinical challenge, affecting 5-10% of women and leading to complications for both maternal well-being and fetal development. At the heart of these complications is endothelial dysfunction, with oxidative stress emerging as a pivotal causative factor. The reduction in nitric oxide (NO) bioavailability is a vital indicator of this dysfunction, culminating in blood pressure dysregulation. In the therapeutic context, although antihypertensive medications are commonly used, they come with inherent concerns related to maternal-fetal safety, and a percentage of women do not respond to these therapies. Therefore, alternative strategies that directly address the pathophysiology of HDPs are required. This article focuses on the potential of the nitrate-nitrite-NO pathway, abundantly present in dark leafy greens and beetroot, as an alternative approach to treating HDPs. The objective of this review is to discuss the prospective antioxidant role of nitrate. We hope our discussion paves the way for using nitrate to improve endothelial dysfunction and control oxidative stress, offering a potential therapy for managing HDPs.


Sujet(s)
Hypertension artérielle gravidique , Nitrates , Monoxyde d'azote , Nitrites , Stress oxydatif , Humains , Stress oxydatif/effets des médicaments et des substances chimiques , Grossesse , Nitrates/métabolisme , Femelle , Monoxyde d'azote/métabolisme , Nitrites/métabolisme , Hypertension artérielle gravidique/traitement médicamenteux , Hypertension artérielle gravidique/métabolisme , Antioxydants , Beta vulgaris
3.
Clin Nutr ; 43(7): 1642-1646, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38805867

RÉSUMÉ

BACKGROUND & AIMS: The post-menopausal period represents a noteworthy stage in a woman's life characterized by hormonal shifts that can influence diverse biological processes encompassing energy metabolism and physical performance. NO3- effects on physical performance in 50-65 years old postmenopausal women after short-term supplementation remain unknown. METHODS: This is a randomized, double-blind, placebo-controlled, crossover study. After two sessions in non-consecutive days of familiarization tests, fifteen post-menopausal women aged between 50 and 65 were enrolled in this study. The trial consisted of two eight-day arms: a) NO3- -70 mL of beetroot juice (BRJ) with ˜400 mg of NO3-, and b) placebo (PLA) -70 mL of BRJ NO3- depleted. Both interventions were obtained from the same manufacturer's product, presenting the same organoleptic properties. After this period, five physical performance tests (handgrip strength, arm curl, sit-to-stand, agility and dynamic balance and 6-min walk test (6MWT)) were applied. RESULTS: Fourteen participants completed all experimental protocols, including a minimum seven-day washout period between protocols. NO2- plasma concentrations were consistently elevated in the NO3- condition at 0.41 (0.40) µM compared to the PLA at 0.18 (0.18) µM (p < 0.001). The 6MWT showed higher values in BRJ with NO3- condition (19.6 m [95%CI: 1.33 to 37.88]; p = 0.038), while the other physical performance tests did not show significant difference between conditions (p > 0.05). CONCLUSIONS: Our findings suggest benefits in the physical performance of activities with longer durations, indicating that the adaptation caused by ingestion of NO3- may be related to the cardiorespiratory capacity.


Sujet(s)
Études croisées , Jus de fruits et de légumes , Nitrates , Performance fonctionnelle physique , Post-ménopause , Humains , Femelle , Méthode en double aveugle , Adulte d'âge moyen , Nitrates/administration et posologie , Nitrates/sang , Sujet âgé , Projets pilotes , Beta vulgaris/composition chimique , Compléments alimentaires , Force de la main/physiologie
4.
Antioxidants (Basel) ; 13(3)2024 Feb 20.
Article de Anglais | MEDLINE | ID: mdl-38539788

RÉSUMÉ

Nitrite is a nitric oxide (NO) metabolite, which may be bioactivated to generate NO in vivo and supplement endogenous NO formation, especially in cardiovascular and metabolic diseases. However, it is not known whether treatment with oral nitrite results in the accumulation of NO metabolites in different organs. Moreover, treatment with omeprazole, an inhibitor of gastric acid secretion, severely affects the gastric formation of S-nitrosothiols induced with oral nitrite treatment. However, no previous study has examined whether omeprazole affects the nitrite-induced accumulation of NO metabolites in different organs. This study examined in rats the effects of oral sodium nitrite treatment (15 mg/kg via gavage for 1 or 7 days) associated with omeprazole (10 mg/kg or vehicle) on nitrite and nitrate and nitrosylated species (RXNO) concentrations (measured using ozone-based chemiluminescence methods) assessed in the plasma, aorta, heart, liver, brain, and muscle. While our results showed that NO metabolite accumulation in different organs is not uniform, we found that the skeletal muscle, the heart, and the liver accumulate NO metabolites, particularly RXNO. This response was significantly attenuated by omeprazole in the heart and in the skeletal muscle. Together, these findings may indicate that the skeletal muscle, the heart, and the liver are major reservoir sites for NO metabolites after oral nitrite treatment, with major increases in nitrosylated species.

5.
Front Genet ; 15: 1293082, 2024.
Article de Anglais | MEDLINE | ID: mdl-38469120

RÉSUMÉ

Impaired nitric oxide (NO) formation may be associated with endothelial dysfunction and increased cardiovascular disease risk in preeclampsia (PE). Functional single-nucleotide polymorphisms (SNPs) of nitric oxide synthase 3 (NOS3) (rs3918226) and guanylate cyclase 1, soluble, alpha 3 (GUCY1A3) (rs7692387) increase susceptibility to the adverse consequences due to inadequate generation of NO by the endothelium. However, no previous study has examined whether these SNPs affect NO formation in healthy pregnancy and in gestational hypertension (GH) and PE. Here, we compared the alleles and genotypes of NOS3 (rs3918226) and GUCY1A3 (rs7692387) SNPs in normotensive pregnant women (NP, n = 153), in GH (n = 96) and PE (n = 163), and examined whether these SNPs affect plasma nitrite concentrations (a marker of NO formation) in these groups. We further examined whether the interaction among SNP genotypes is associated with GH and PE. Genotypes were determined using TaqMan allele discrimination assays, and plasma nitrite concentrations were determined by an ozone-based chemiluminescence assay. Multifactor dimensionality reduction was used to examine the interactions among SNP genotypes. Regarding NOS3 rs3918226, the CT genotype (p = 0.046) and T allele (p = 0.020) were more frequent in NP than in GH, and GH patients carrying the CT+TT genotypes showed lower nitrite concentrations than NP carrying the CT+TT genotypes (p < 0.05). Regarding GUCY1A3 rs7692387, the GA genotype (p = 0.013) and A allele (p = 0.016) were more frequent in PE than in NP, and NP women carrying the GG genotype showed higher nitrite concentrations than GH or PE patients carrying the GG genotype (p < 0.05). However, we found no significant interactions among genotypes for these functional SNPs to be associated with GH or PE. Our novel findings suggest that NOS3 rs3918226 and GUCY1A3 rs7692387 may affect NO formation and association with hypertensive disorders of pregnancy.

6.
Mol Cell Biochem ; 2024 Feb 01.
Article de Anglais | MEDLINE | ID: mdl-38302836

RÉSUMÉ

The use of inhibitors of gastric acid secretion (IGAS), especially proton pump inhibitors (PPI), has been associated with increased cardiovascular risk. While the mechanisms involved are not known, there is evidence supporting increased oxidative stress, a major activator of matrix metalloproteinases (MMP), as an important player in such effect. However, there is no study showing whether other IGAS such as histamine H2-receptor blockers (H2RB) cause similar effects. This study aimed at examining whether treatment with the H2RB ranitidine promotes oxidative stress resulting in vascular MMP activation and corresponding functional and structural alterations in the vasculature, as compared with those found with the PPI omeprazole. Male Wistar rats were treated (4 weeks) with vehicle (2% tween 20), omeprazole (10 mg/Kg/day; i.p.) or ranitidine (100 mg/Kg/day; gavage). Then the aorta was collected to perform functional, biochemical, and morphometric analysis. Both ranitidine and omeprazole increased gastric pH and oxidative stress assessed in situ with the fluorescent dye dihydroethidium (DHE) and with lucigenin chemiluminescence assay. Both IGAS augmented vascular activated MMP-2. These findings were associated with aortic remodeling (increased media/lumen ratio and number of cells/µm2). Both IGAS also impaired the endothelium-dependent relaxation induced by acetylcholine (isolated aortic ring preparation). This study provides evidence that the H2RB ranitidine induces vascular dysfunction, redox alterations, and remodeling similar to those found with the PPI omeprazole. These findings strongly suggest that IGAS increase oxidative stress and matrix metalloproteinase-2 activity leading to vascular remodeling, which helps to explain the increased cardiovascular risk associated with the use of those drugs.

7.
Free Radic Biol Med ; 211: 12-23, 2024 02 01.
Article de Anglais | MEDLINE | ID: mdl-38092272

RÉSUMÉ

BACKGROUND: The increase in blood pressure (BP) levels in the postmenopausal period can be partly explained by the decrease in nitric oxide synthases (NOS). OBJECTIVE: To investigate the acute and one-week effects of beetroot juice nitrate-rich (BRJ-NO3-rich) ingestion on cardiovascular and autonomic performance in response to submaximal aerobic exercise in postmenopausal women with systemic arterial hypertension (SAH) who are physically inactive. METHODS: Fourteen postmenopausal women with SAH [mean (SD) age: 59(4) y; BMI (kg/m2): 29.2(3.1)] completed submaximal aerobic exercise bouts after an acute and a one-week intervention with BRJ in a placebo-controlled, randomized, triple-blind, crossover design. Participants ingested either BRJ (800 mg of NO3-) or placebo acutely and drank either BRJ (400 mg of NO3-) or placebo every day for the next six days. After two and ½ hours, they performed a session of aerobic submaximal aerobic exercise, and their systolic BP (SBP) and diastolic BP (DBP), flow-mediated dilation (FMD), heart rate (HR) recovery, and HR variability were measured. RESULTS: In the post-exercise recovery period, SBP dropped significantly in the BRJ-NO3-rich group (-9.28 mmHg [95%CI: -1.68 to -16.88] ES: -0.65, p = 0.019) compared to placebo after acute ingestion. The FMD values increased after acute BRJ-NO3-rich on post-exercise (3.18 % [0.36 to 5.99] ES: 0.87, p = 0.031). After the one-week intervention, FMD values were higher in the BRJ-NO3-rich group before (4.5 % [1.62 to 7.37] ES: 1.21, p = 0.005) and post-exercise measurements (4.2 % [1.52 to 6.87] ES: 1.22, p = 0.004) vs. placebo. HRV indices with remarkable parasympathetic modulation to heart recovered faster on the BRJ-NO3-rich group than placebo group. No between-group differences were identified in values of HR post-exercise recovery in the 30s, 60s, 120s, 180s, and 300s. CONCLUSIONS: Acute and short-term BRJ-NO3-rich ingestion may enhance cardiovascular and autonomic behavior in response to aerobic exercise in postmenopausal women diagnosed with SAH. CLINICAL TRIAL REGISTRY NUMBER: https://clinicaltrials.gov/ct2/show/NCT05384340.


Sujet(s)
Beta vulgaris , Hypertension artérielle , Humains , Femelle , Adulte d'âge moyen , Nitrates/pharmacologie , Post-ménopause , Compléments alimentaires , Jus de fruits et de légumes , Hypertension artérielle/thérapie , Exercice physique/physiologie , Pression sanguine , Consommation alimentaire , Méthode en double aveugle , Études croisées
8.
J Periodontal Res ; 58(5): 1006-1019, 2023 Oct.
Article de Anglais | MEDLINE | ID: mdl-37482954

RÉSUMÉ

OBJECTIVE: To determine whether Bifidobacterium animalis subspecies lactis HN019 (B. lactis HN019) can reduce the sequelae of experimental periodontitis (EP) in rats modulating systemic parameters. BACKGROUND: This study evaluated the effects of probiotic therapy (PROB) in the prevention of local and systemic damage resulting from EP. METHODS: Forty-eight rats were allocated into four groups: C (control), PROB, EP, and EP-PROB. PROB (1 × 1010 CFU/mL) administration lasted 8 weeks and PE was induced on the 7th week by placing ligature on the animals' lower first molars. All animals were euthanized in the 9th week of the experiment. Biomolecular analyses, RT-PCR, and histomorphometric analyses were performed. The data obtained were analyzed statistically (ANOVA, Tukey, p < .05). RESULTS: The EP group had higher dyslipidemia when compared to the C group, as well as higher levels of insulin resistance, proteinuria levels, percentages of systolic blood pressure, percentage of fatty hepatocytes in the liver, and expression of adipokines was up-regulated (LEPR, NAMPT, and FABP4). All these parameters (except insulin resistance, systolic blood pressure, LEPR and FABP4 gene expression) were reduced in the EP-PROB group when compared to the EP group. The EP group had lower villus height and crypt depth, as well as a greater reduction in Bacteroidetes and a greater increase in Firmicutes when compared to the EP-PROB group. Greater alveolar bone loss was observed in the EP group when compared to the EP-PROB group. CONCLUSION: Bifidobacterium lactis HN019 can reduce the sequelae of EP in rats modulating intestinal parameters, attenuating expression of lipogenic genes and hepatic steatosis.


Sujet(s)
Bifidobacterium animalis , Stéatose hépatique , Insulinorésistance , Parodontite , Probiotiques , Rats , Animaux , Bifidobacterium animalis/physiologie , Probiotiques/usage thérapeutique , Parodontite/prévention et contrôle , Muqueuse intestinale
9.
Biochem Pharmacol ; 212: 115571, 2023 06.
Article de Anglais | MEDLINE | ID: mdl-37127250

RÉSUMÉ

The unsatisfactory rates of adequate blood pressure control among patients receiving antihypertensive treatment calls for new therapeutic strategies to treat hypertension. Several studies have shown that oral sodium nitrite exerts significant antihypertensive effects, but the mechanisms underlying these effects remain unclear. While these mechanisms may involve nitrite-derived S-nitrosothiols, their implication in important alterations associated with hypertension, such as aberrant α1-adrenergic vasoconstriction, has not yet been investigated. Here, we examined the effects of oral nitrite treatment on vascular responses to the α1-adrenergic agonist phenylephrine in two-kidney, one clip (2K1C) hypertensive rats and investigated the potential underlying mechanisms. Our results show that treatment with oral sodium nitrite decreases blood pressure and prevents the increased α1-adrenergic vasoconstriction in 2K1C hypertensive rats. Interestingly, we found that these effects require vascular protein S-nitrosylation, and to investigate the specific S-nitrosylated proteins we performed an unbiased nitrosoproteomic analysis of vascular smooth muscle cells (VSMCs) treated with the nitrosylating compound S-nitrosoglutathione (GSNO). This analysis revealed that GSNO markedly increases the nitrosylation of calcium/calmodulin-dependent protein kinase II γ (CaMKIIγ), a multifunctional protein that mediates the α1-adrenergic receptor signaling. This result was associated with reduced α1-adrenergic receptor-mediated CaMKIIγ activity in VSMCs. We further tested the relevance of these findings in vivo and found that treatment with oral nitrite increases CaMKIIγ S-nitrosylation and blunts the increased CaMKIIγ activity induced by phenylephrine in rat aortas. Collectively, these results are consistent with the idea that oral sodium nitrite treatment increases vascular protein S-nitrosylation, including CaMKIIγ as a target, which may ultimately prevent the increased α1-adrenergic vasoconstriction induced by hypertension. These mechanisms may help to explain the antihypertensive effects of oral nitrite and hold potential implications in the therapy of hypertension and other cardiovascular diseases associated with abnormal α1-adrenergic vasoconstriction.


Sujet(s)
Hypertension artérielle , Nitrite de sodium , Rats , Animaux , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Antihypertenseurs/pharmacologie , Antihypertenseurs/usage thérapeutique , Vasoconstriction , Calcium , Agents adrénergiques/pharmacologie , Agents adrénergiques/usage thérapeutique , Hypertension artérielle/induit chimiquement , Hypertension artérielle/traitement médicamenteux , Hypertension artérielle/prévention et contrôle , Phényléphrine/pharmacologie , Récepteurs adrénergiques/usage thérapeutique , Récepteurs alpha-1 adrénergiques/métabolisme
10.
J Periodontol ; 94(11): 1363-1375, 2023 Nov.
Article de Anglais | MEDLINE | ID: mdl-37057371

RÉSUMÉ

BACKGROUND: This study evaluated the systemic (intestine and adipose tissue) and local (periodontal tissues) impact of probiotic therapy in rats with metabolic syndrome (MS) associated or not with periodontitis (PE). METHODS: Forty-eight rats received a high-fat diet for induction of MS for 16 weeks. They were subdivided into groups with (+) and without (-) PE, receiving (*) or not (**) receiving probiotics (PROB): MS (-**), MSP (-*), MSPE (+**), and MSPEP (+*). PROB administration (Bifidobacterium animalis subsp. lactis HN019) started on the 8th week of the study and PE was induced on the 14th week by placing ligature on the animals' lower first molars. Euthanasia occurred in the 16th week. Biomolecular, immunoenzymatic assays, and histomorphometric analyses were performed. The data obtained were statistically analyzed (ANOVA, Tukey, p < 0.05). RESULTS: The MSPEP group exhibited reduced alveolar bone loss when compared with the MSPE group, as well as lower levels of hepatic steatosis and proteinuria (p < 0.05). In the intestinal environment, the MSPE group exhibited significantly lower villus height and crypt depth, as well as a greater increase in Bacillota when compared with the MSPEP group (p < 0.05). The MSPEP group showed lower adipokine gene expression (LEPR, NAMPT, and FABP4) in adipose tissue than the MSPE group (p < 0.05). CONCLUSION: The probiotic B. lactis HN019 reduced the severity of experimental periodontitis and modulated the expression of lipogenic genes and intestinal morphological and microbiological parameters in rats with MS.


Sujet(s)
Bifidobacterium animalis , Syndrome métabolique X , Parodontite , Probiotiques , Rats , Animaux , Syndrome métabolique X/complications , Parodontite/thérapie , Parodontite/métabolisme , Intestins/microbiologie , Probiotiques/usage thérapeutique , Probiotiques/pharmacologie
11.
Trials ; 24(1): 94, 2023 Feb 07.
Article de Anglais | MEDLINE | ID: mdl-36750904

RÉSUMÉ

BACKGROUND: There is no evidence of the use of beetroot juice with a previously recommended dose of nitrate (NO3) (> 300 mg) on the cardiovascular performance during and recovery following exercise in postmenopausal women with systemic arterial hypertension (SAH). METHODS: We will investigate the effects of beetroot juice rich in NO3 acutely (800 mg) and during a week with daily doses (400 mg) on blood pressure, heart rate (HR), cardiac autonomic control, endothelial function, inflammatory, hormonal, and stress biomarkers oxidative stress and enzymes involved in nitric oxide synthesis and mitochondrial regulation, under resting conditions, as well as mediated by submaximal aerobic exercise sessions. Through a randomized, crossover, triple-blind, placebo-controlled clinical trial, 25 physically inactive women with SAH will undergo an acute and 1-week trial, each with two intervention protocols: (1) placebo and (2) beetroot, in which will ingest beet juice with or without NO3 in its composition with a 7-day washout interval. On collection days, exercise will be performed on a treadmill for 40 min at a speed corresponding to 65-70% of VO2peak. The collection of variables (cardiovascular, autonomic, and blood samples for molecular analyses) of the study will take place at rest (135 min after ingestion of the intervention), during exercise (40 min), and in the effort recovery stage (during 60 min) based on previously validated protocols. The collections were arranged so that the measurement of one variable does not interfere with the other and that they have adequate intervals between them. DISCUSSION: The results of this research may help in the real understanding of the nutritional compounds capable of generating safety to the cardiovascular system during physical exercise, especially for women who are aging and who have cardiovascular limitations (e.g., arterial hypertension) to perform physical exercise. Therefore, our results will be able to help specific nutritional recommendations to optimize cardiovascular health. TRIAL REGISTRATION: ClinicalTrials.gov NCT05384340. Registered on May 20, 2022.


Sujet(s)
Beta vulgaris , Système cardiovasculaire , Hypertension artérielle , Humains , Femelle , Nitrates/analyse , Nitrates/usage thérapeutique , Nitrites/analyse , Post-ménopause , Exercice physique/physiologie , Compléments alimentaires , Études croisées , Méthode en double aveugle , Essais contrôlés randomisés comme sujet
12.
Curr Issues Mol Biol ; 44(12): 6333-6345, 2022 Dec 14.
Article de Anglais | MEDLINE | ID: mdl-36547093

RÉSUMÉ

Anesthesia with propofol is frequently associated with hypotension. The TRPA1 gene contributes to the vasodilator effect of propofol. Hypotension is crucial for anesthesiologists because it is deleterious in the perioperative period. We tested whether the TRPA1 gene polymorphisms or haplotypes interfere with the hypotensive responses to propofol. PCR-determined genotypes and haplotype frequencies were estimated. Nitrite, nitrates, and NOx levels were measured. Propofol induced a more expressive lowering of the blood pressure (BP) without changing nitrite or nitrate levels in patients carrying CG+GG genotypes for the rs16937976 TRPA1 polymorphism and AG+AA genotypes for the rs13218757 TRPA1 polymorphism. The CGA haplotype presented the most remarkable drop in BP. Heart rate values were not impacted. The present exploratory analysis suggests that TRPA1 genotypes and haplotypes influence the hypotensive responses to propofol. The mechanisms involved are probably other than those related to NO bioavailability. With better genetic knowledge, planning anesthesia with fewer side effects may be possible.

13.
Redox Biol ; 54: 102362, 2022 08.
Article de Anglais | MEDLINE | ID: mdl-35709537

RÉSUMÉ

In blood, the majority of endothelial nitric oxide (NO) is scavenged by oxyhemoglobin, forming nitrate while a small part reacts with dissolved oxygen to nitrite; another fraction may bind to deoxyhemoglobin to generate nitrosylhemoglobin (HbNO) and/or react with a free cysteine to form a nitrosothiol. Circulating nitrite concentrations in healthy individuals are 200-700 nM, and can be even lower in patients with endothelial dysfunction. Those levels are similar to HbNO concentrations ([HbNO]) recently reported, whereby EPR-derived erythrocytic [HbNO] was lower in COVID-19 patients compared to uninfected subjects with similar cardiovascular risk load. We caution the values reported may not reflect true (patho)physiological concentrations but rather originate from complex chemical interactions of endogenous nitrite with hemoglobin and ascorbate/N-acetylcysteine. Using an orthogonal detection method, we find baseline [HbNO] to be in the single-digit nanomolar range; moreover, we find that these antioxidants, added to blood collection tubes to prevent degradation, artificially generate HbNO. Since circulating nitrite also varies with lifestyle, dietary habit and oral bacterial flora, [HbNO] may not reflect endothelial activity alone. Thus, its use as early marker of NO-dependent endothelial dysfunction to stratify COVID-19 patient risk may be premature. Moreover, oxidative stress not only impairs NO formation/bioavailability, but also shifts the chemical landscape into which NO is released, affecting its downstream metabolism. This compromises the endothelium's role as gatekeeper of tissue nutrient supply and modulator of blood cell function, challenging the body's ability to maintain redox balance. Further studies are warranted to clarify whether the nature of vascular dysfunction in COVID-19 is solely of endothelial nature or also includes altered erythrocyte function.


Sujet(s)
COVID-19 , Nitrites , Spectroscopie de résonance de spin électronique , Endothélium/métabolisme , Hémoglobines/métabolisme , Humains , Monoxyde d'azote/métabolisme , Nitrites/métabolisme , Oxydoréduction ,
14.
Biomolecules ; 12(5)2022 04 19.
Article de Anglais | MEDLINE | ID: mdl-35625532

RÉSUMÉ

Patients with COVID-19 predominantly have a respiratory tract infection and acute lung failure is the most severe complication. While the molecular basis of SARS-CoV-2 immunopathology is still unknown, it is well established that lung infection is associated with hyper-inflammation and tissue damage. Matrix metalloproteinases (MMPs) contribute to tissue destruction in many pathological situations, and the activity of MMPs in the lung leads to the release of bioactive mediators with inflammatory properties. We sought to characterize a scenario in which MMPs could influence the lung pathogenesis of COVID-19. Although we observed high diversity of MMPs in lung tissue from COVID-19 patients by proteomics, we specified the expression and enzyme activity of MMP-2 in tracheal-aspirate fluid (TAF) samples from intubated COVID-19 and non-COVID-19 patients. Moreover, the expression of MMP-8 was positively correlated with MMP-2 levels and possible shedding of the immunosuppression mediator sHLA-G and sTREM-1. Together, overexpression of the MMP-2/MMP-8 axis, in addition to neutrophil infiltration and products, such as reactive oxygen species (ROS), increased lipid peroxidation that could promote intensive destruction of lung tissue in severe COVID-19. Thus, the inhibition of MMPs can be a novel target and promising treatment strategy in severe COVID-19.


Sujet(s)
COVID-19 , Matrix metalloproteinase 2 , Antigènes HLA-G , Humains , Immunité , Matrix metalloproteinase 2/métabolisme , Matrix metalloproteinase 8/métabolisme , Stress oxydatif , SARS-CoV-2
15.
J Periodontol ; 93(2): e1-e12, 2022 02.
Article de Anglais | MEDLINE | ID: mdl-34374081

RÉSUMÉ

BACKGROUND: This study evaluated the effects of Bifidobacterium animalis subsp. lactis HN019 (B. lactis HN019) in the development of periodontitis (PE), associated or not with metabolic syndrome, (MS) in rats. METHODS: Ninety-six rats were grouped according to a food protocol: high-fat diet for induction of MS or standard diet for the control groups (C). They were subdivided into groups with (+) and without (-) PE, receiving (*) or not (**) probiotic (PROB): C-**, CP-*, PE+**, PEP+*, MS- MSP-*, MSPE+**, and MSPEP+*. PROB administration started on the eighth week of the study and PE was induced on the 14th week by placing ligature on the animals' lower first molars. Euthanasia occurred in the 16th week. Biomolecular analyzes, immunoenzymatic assays, and microtomographic analyses were performed. The data obtained were analyzed statistically (P < 0.05). RESULTS: The PEP and MSPEP groups showed lower levels of alveolar bone loss when compared with the PE and MSPE groups, respectively (P < 0.05). The immunoenzymatic analysis showed higher levels of interleukin (IL)-1ß and a higher receptor activator of NF-kappaB ligand (RANKL)/osteoprotegerin (OPG) ratio in the MSPE group when compared with the MSPEP group (P < 0.05). The PEP group showed lower levels of tumor necrosis factor (TNF)-α and IL-6 when compared with the PE group. The use of PROB attenuated dyslipidemia parameters in animals with MS, with or without PE. CONCLUSION: B. lactis HN019 reduced more significantly the severity of PE in rats with MS, modulating both systemic metabolic and immunoinflammatory parameters in periodontal tissues.


Sujet(s)
Résorption alvéolaire , Bifidobacterium animalis , Syndrome métabolique X , Parodontite , Probiotiques , Résorption alvéolaire/imagerie diagnostique , Résorption alvéolaire/métabolisme , Résorption alvéolaire/prévention et contrôle , Animaux , Bifidobacterium animalis/métabolisme , Syndrome métabolique X/complications , Ostéoprotégérine/analyse , Parodontite/métabolisme , Probiotiques/pharmacologie , Probiotiques/usage thérapeutique , Ligand de RANK/métabolisme , Rats , Rat Wistar , Facteur de nécrose tumorale alpha/métabolisme
16.
Basic Clin Pharmacol Toxicol ; 130(2): 277-287, 2022 Feb.
Article de Anglais | MEDLINE | ID: mdl-34825477

RÉSUMÉ

Anaesthesia with propofol is frequently associated with hypotension, which is at least partially attributable to increased nitric oxide (NO) formation derived from the activation of protein kinase C (PKC)/endothelial NO synthase (NOS3) axis. In this cross-sectional study, we tested whether PRKCA (which encodes PKCα) polymorphisms, or haplotypes, and interactions among PRKCA and NOS3 polymorphisms affect the hypotensive responses to propofol. We collected venous blood samples from 164 patients before and 10 min after propofol administration. Genotypes were determined by PCR and haplotype frequencies were estimated. Nitrite and NOx (nitrites+nitrates) levels were measured by using an ozone-based chemiluminescence assay and the Griess reaction, respectively. We used multifactor dimensionality reduction to test interactions among PRKCA and NOS3 polymorphisms. Propofol promoted enhanced blood pressure-lowering effects and increased nitrite levels in subjects carrying GA + AA genotypes for the rs16960228 and TC + CC genotypes for the rs1010544 PRKCA polymorphisms, and the CCG haplotype. Moreover, genotypes for the rs1010544 PRKCA polymorphism were associated with higher or lower blood pressure decreases in response to propofol depending on the genotypes for the rs2070744 NOS3 polymorphism. Our findings suggest that PRKCA genotypes and haplotypes impact the hypotensive responses to propofol, possibly by modifying NO bioavailability, and that PRKCA-NOS3 interactions modify the blood pressure-lowering effects of propofol.


Sujet(s)
Hypotension artérielle/induit chimiquement , Nitric oxide synthase type III/génétique , Propofol/effets indésirables , Protein kinase C-alpha/génétique , Adulte , Sujet âgé , Anesthésiques intraveineux/administration et posologie , Anesthésiques intraveineux/effets indésirables , Études transversales , Femelle , Génotype , Haplotypes , Humains , Hypotension artérielle/génétique , Mâle , Adulte d'âge moyen , Monoxyde d'azote/métabolisme , Propofol/administration et posologie
17.
Chem Biol Interact ; 349: 109658, 2021 Nov 01.
Article de Anglais | MEDLINE | ID: mdl-34543659

RÉSUMÉ

Nitric oxide (NO) metabolites have physiological and pharmacological importance and increasing their tissue concentrations may result in beneficial effects. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) has antioxidant properties that may improve NO bioavailability. Moreover, tempol increases oral nitrite-derived gastric formation of S-nitrosothiols (RSNO). We hypothesized that pretreatment with tempol may further increase tissue concentrations of NO-related species after oral nitrite administration and therefore we carried out a time-dependent analysis of how tempol affects the concentrations of NO metabolites in different tissues after oral nitrite administration to rats. NO metabolites (nitrate, nitrite and RSNO) were assessed by ozone-based reductive chemiluminescence assays in plasma, stomach, aorta, heart and liver samples obtained from anesthetized rats at baseline conditions and 15 min, 30 min, 2 h or 24 h after oral nitrite (15 mg/kg) was administered to rats pretreated with tempol (18 mg/kg) or vehicle 15 min prior to nitrite administration. Aortic protein nitrosation was assessed by resin-assited capture (SNO-RAC) method. We found that pretreatment with tempol transiently enhanced nitrite-induced increases in nitrite, RSNO and nitrate concentrations in the stomach and in the plasma (all P < 0.05), particularly for 15-30 min, without affecting aortic protein nitrosation. Pretreatment with tempol enhanced nitrite-induced increases in nitrite (but not RSNO or nitrate) concentrations in the heart (P < 0.05). In contrast, tempol attenuated nitrite-induced increases in nitrite, RSNO or nitrate concentrations in the liver. These findings show that pretreatment with tempol affects oral nitrite-induced changes in tissue concentrations of NO metabolites depending on tissue type and does not increase nitrite-induced vascular nitrosation. These results may indicate that oral nitrite therapy aiming at achieving increased nitrosation of cardiovascular targets requires appropriate doses of nitrite and is not optimized by tempol.


Sujet(s)
Antioxydants/pharmacologie , N-oxydes cycliques/pharmacologie , Monoxyde d'azote/métabolisme , Nitrites/administration et posologie , Administration par voie orale , Animaux , Mâle , Nitrates/sang , Nitrites/sang , Rats , Rat Wistar , Marqueurs de spin
18.
Eur J Pharmacol ; 907: 174314, 2021 Sep 15.
Article de Anglais | MEDLINE | ID: mdl-34245745

RÉSUMÉ

L-arginine supplementation increases nitric oxide (NO) formation and bioavailability in hypertension. We tested the possibility that many effects of L-arginine are mediated by increased formation of NO and enhanced nitrite, nitrate and nitrosylated species concentrations, thus stimulating the enterosalivary cycle of nitrate. Those effects could be prevented by antiseptic mouthwash. We examined how the derangement of the enterosalivary cycle of nitrate affects the improvement of endothelial dysfunction (assessed with isolated aortic ring preparation), the antihypertensive (assessed by tail-cuff blood pressure measurement) and the antioxidant effects (assessed with the fluorescent dye DHE) of L-arginine in two-kidney, one-clip hypertension model in rats by using chlorhexidine to decrease the number of oral bacteria and to decrease nitrate reductase activity assessed from the tongue (by ozone-based chemiluminiscence assay). Nitrite, nitrate and nitrosylated species concentrations were assessed (ozone-based chemiluminiscence). Chlorhexidine mouthwash reduced the number of oral bacteria and tended to decrease the nitrate reductase activity from the tongue. Antiseptic mouthwash blunted the improvement of the endothelial dysfunction and the antihypertensive effects of L-arginine, impaired L-arginine-induced increases in plasma nitrite and nitrosylated species concentrations, and blunted L-arginine-induced increases in aortic nitrate concentrations and vascular antioxidant effects. Our results show for the first time that the vascular and antihypertensive effects of L-arginine are prevented by antiseptic mouthwash. These findings show an important new mechanism that should be taken into consideration to explain how the use of antibacterial mouth rinse may affect arterial blood pressure and the risk of developing cardiovascular and other diseases.


Sujet(s)
Antihypertenseurs , Animaux , Chlorhexidine , Nitrites , Rats
19.
Nitric Oxide ; 115: 23-29, 2021 10 01.
Article de Anglais | MEDLINE | ID: mdl-34133975

RÉSUMÉ

INTRODUCTION: The mechanical obstruction and pulmonary vasoconstriction are major determinants of the sudden right ventricular (RV) afterload increases observed during acute pulmonary thromboembolism (APT). Vasodilators and antioxidants agents have been shown to mitigate pulmonary hypertension. We examined whether sodium nitrite and the antioxidant tempol combination could be advantageous in an APT sheep model. METHODS: APT was induced in anesthetized sheep by autologous blood clots (250 mg/kg) into the right atrium. Thirty minutes after APT induction, the animals received a continuous infusion of tempol (1.0 mg/kg/min), increasing sodium nitrite infusion (5, 15, and 50 µmol/kg), or a simultaneous combination of both drugs. Saline was used as a control treatment. Hemodynamic measurements were carried out every 15 min. Also, whole blood nitrite and serum 8-isoprostanes levels were measured. RESULTS: APT induced sustained pulmonary hypertension, increased dp/dtmax, and rate pressure product (RPP). Nitrite or tempol treatments attenuated these increases (P < 0.05). When both drugs were combined, we found a robust reduction in the RV RPP compared with the treatments alone (P < 0.05). The sole nitrite infusion increased blood nitrite concentrations by 35 ± 6 µM (P < 0.05), whereas the nitrite and tempol combination produced higher blood nitrite concentrations by approximately 54 ± 7 µM. Tempol or nitrite infusions, both alone or combined, blunted the increases in 8-isoprostane concentrations observed after APT. CONCLUSIONS: Nitrite and tempol combination protects against APT-induced RV wall stress. The association of both drugs may offer an advantage to treat RV failure during severe APT.


Sujet(s)
Antioxydants/pharmacologie , N-oxydes cycliques/pharmacologie , Ventricules cardiaques/effets des médicaments et des substances chimiques , Hypertension pulmonaire/traitement médicamenteux , Nitrite de sodium/pharmacologie , Maladie aigüe , Animaux , Antioxydants/administration et posologie , N-oxydes cycliques/administration et posologie , Ventricules cardiaques/métabolisme , Hypertension pulmonaire/sang , Hypertension pulmonaire/métabolisme , Mâle , Ovis , Nitrite de sodium/administration et posologie , Marqueurs de spin
20.
Biochem Pharmacol ; 190: 114633, 2021 08.
Article de Anglais | MEDLINE | ID: mdl-34058185

RÉSUMÉ

Proton pump inhibitors (PPI) are commonly used drugs that may increase the cardiovascular risk by mechanisms not entirely known. We examined whether the PPI omeprazole promotes vascular oxidative stress mediated by xanthine oxidoreductase (XOR) leading to activation of matrix metalloproteinases (MMPs) and vascular remodeling. We studied Wistar rats treated with omeprazole (or vehicle) combined with the XOR inhibitor allopurinol (or vehicle) for four weeks. Systolic blood pressure (SBP) measured by tail-cuff plethysmography was not affected by treatments. Omeprazole treatment increased the aortic cross-sectional area and media/lumen ratio by 25% (P < 0.05). Omeprazole treatment decreased gastric pH and induced vascular remodeling accompanied by impaired endothelium-dependent aortic responses (assessed with isolated aortic ring preparation) to acetylcholine (P < 0.05). Omeprazole increased vascular active MMP-2 expression and activity assessed by gel zymography and in situ zymography, respectively (P < 0.05). Moreover, omeprazole enhanced vascular oxidative stress assessed in situ with the fluorescent dye DHE and with the lucigenin chemiluminescence assay (both P < 0.05). All these biochemical changes caused by omeprazole were associated with increased vascular XOR activity (but not XOR expression assessed by Western blot) and treatment with allopurinol fully prevented them (all P < 0.05). Importantly, treatment with allopurinol prevented the vascular dysfunction and remodeling caused by omeprazole. Our results suggest that the long-term use of omeprazole induces vascular dysfunction and remodeling by promoting XOR-derived reactive oxygen species formation and MMP activation. These findings provide evidence of a new mechanism that may underlie the unfavorable cardiovascular outcomes observed with PPI therapy. Clinical studies are warranted to validate our findings.


Sujet(s)
Matrix metalloproteinases/métabolisme , Oméprazole/pharmacologie , Xanthine dehydrogenase/métabolisme , Allopurinol/pharmacologie , Animaux , Antiulcéreux/pharmacologie , Aorte/effets des médicaments et des substances chimiques , Antienzymes/pharmacologie , Régulation de l'expression des gènes codant pour des enzymes/effets des médicaments et des substances chimiques , Concentration en ions d'hydrogène , Mâle , Matrix metalloproteinases/génétique , Répartition aléatoire , Rats , Rat Wistar , Espèces réactives de l'oxygène , Remodelage vasculaire , Xanthine dehydrogenase/génétique
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