Nitric oxide : biology and chemistry最新文献

{"title":"Corrigendum to “Catestatin alleviates PASMC phenotypic switching-mediated pulmonary arterial remodeling in a rat model of MCT-induced pulmonary arterial hypertension by promoting endothelium-derived NO synthesis” [Nitric Oxide158 (2025) 93–105]","authors":"Zheyu Liu , Bo Cui , Hao Ju , Tuantuan Tan , Jinchun Wu , Manqi Yang , Saeed Kashkooli , Mian Cheng , Gang Wu , Tao Liu","doi":"10.1016/j.niox.2025.08.002","DOIUrl":"10.1016/j.niox.2025.08.002","url":null,"abstract":"","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"158 ","pages":"Pages 132-133"},"PeriodicalIF":3.2,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitrate-dependent changes in the primary and lateral root growth in wheat seedlings require the coordinated action of auxin, calcium and nitric oxide","authors":"Sandeep B. Adavi ,&nbsp;Lekshmy Sathee ,&nbsp;Rakesh Pandey ,&nbsp;Prachi Yadav","doi":"10.1016/j.niox.2025.08.003","DOIUrl":"10.1016/j.niox.2025.08.003","url":null,"abstract":"<div><div>Nitrate (NO₃⁻), besides serving as a major N source, also acts as a signalling molecule in plant growth and development. Studies on NO₃⁻ dependent regulation of root growth in wheat (<em>Triticum aestivum</em>) are mostly limited to morphophysiological changes, while the underlying signalling mechanisms remain largely unexplored. To bridge this gap, the present study aims to get a mechanistic understanding of the NO₃⁻ dependent regulation of root growth in wheat seedlings. For this, uniformly germinated two days old wheat seedlings were exposed to nitric oxide (NO) donor sodium nitroprusside (SNP), auxin source Indole-3-butyric acid (IBA), calcium chloride as source of calcium (Ca²⁺), NO scavenger 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), polar auxin transport inhibitor 2,3,5-triiodobenzoic acid (TIBA) and calcium chelator ethylene glycol-bis (β-aminoethyl ether)-N,N,N′,N'-tetraacetic acid (EGTA) with NO₃⁻ as a major determinant. After seven days, root traits were analyzed, and a tissue localization assay was performed using Fluo-3 AM, DAF-FM, and salkowski reagents to visualize the distribution of Ca²⁺, NO, and indole-3-acetic acid (IAA) in root tissues, respectively. The study reveals that the cross-talk of nitric oxide (NO), auxin and calcium (Ca²⁺) modulates NO₃⁻ regulated root growth in wheat seedlings. The changes in cytosolic Ca²⁺ concentration ([Ca²⁺]_cyt) are a major mediator in the regulation of root growth. High NO₃⁻ (5 mM) in combination with exogenous IBA and Ca²⁺ suppresses the root growth, with ethylene acting downstream of [Ca²⁺]_cyt. We observed a synergistic effect between NO and endogenous IAA (Indole-3-acetic acid) in lateral root (LR) growth. In LRs, the external NO₃⁻ enhances the NO production, which is further augmented by the elevated [Ca²⁺]_cyt levels. Our results indicate that endogenous IAA plays a pivotal role in regulating root hair development on LR with NO and [Ca²⁺]_cyt functioning downstream of the signalling cascade. However, the high NO₃⁻ was found to counteract the root hair formation by importing the shoot-derived auxin. These findings provide valuable insights into the intricate signalling interactions between nitric oxide, auxin, and calcium in NO₃⁻ regulated root development in wheat, with potential targets for enhancing nutrient uptake efficiency. Further work is necessary to identify downstream signalling components and examine how shoot-to-root signalling modulates the root architectures under different NO₃⁻ regimes.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 11-22"},"PeriodicalIF":3.2,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential role of brain nitric oxide in inhibiting α7 nicotinic acetylcholine receptor-mediated suppression of the micturition reflex in rats","authors":"Nobutaka Shimizu ,&nbsp;Takahiro Shimizu ,&nbsp;Mio Togo ,&nbsp;Youichirou Higashi ,&nbsp;Satoshi Fukata ,&nbsp;Keiji Inoue ,&nbsp;Motoaki Saito","doi":"10.1016/j.niox.2025.07.003","DOIUrl":"10.1016/j.niox.2025.07.003","url":null,"abstract":"<div><div>Brain nitric oxide (NO), produced by NO synthase (NOS), exerts both facilitatory and inhibitory effects on micturition. A functional relationship between NO and nicotinic acetylcholine receptors (nAChRs) has been indicated, and we previously reported that stimulation of brain α7 nAChR suppresses the micturition reflex in rats. In this study, we investigated which brain NOS isozyme is involved in micturition regulation and how NO influences α7 nAChR-mediated suppression. Cystometry was performed in urethane-anesthetized male rats using a bladder catheter. SNAP (NO donor), <span>l</span>-NAME (NOS inhibitor), 3-bromo-7-nitroindazole (neuronal NOS inhibitor), or BYK191023 (inducible NOS inhibitor) was administered intracerebroventricularly (icv) 3 h after the surgery. In some rats, the effects of pre-treated SNAP or <span>l</span>-NAME on PHA568487 (α7 nAChR agonist, icv)-induced responses were assessed. Intercontraction intervals (ICI)—the interval between two voiding bladder contractions—were recorded starting 1 h before the first icv administration. SNAP (30 nmol/rat) shortened ICI, whereas <span>l</span>-NAME (100 nmol/rat) and 3-bromo-7-nitroindazole (100 nmol/rat) prolonged ICI; BYK191023 had no effect. PHA568487 (1 nmol/rat) induced ICI prolongation, but this response was suppressed by SNAP (10 nmol/rat). At a lower dose (0.3 nmol/rat), PHA568487 had no effect on ICI unless <span>l</span>-NAME (30 nmol/rat) was pre-administered, which then revealed its significant ICI-prolonging effect. These findings suggest a possibility that brain endogenous NO, particularly from neuronal NOS, may be involved in the inhibition of brain α7 nAChR-mediated suppression of the micturition reflex in rats.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"158 ","pages":"Pages 116-123"},"PeriodicalIF":3.2,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitric oxide as a biomarker for patients with endometriosis: a systematic review and meta-analysis","authors":"Kelly Campara ,&nbsp;Patrícia Rodrigues ,&nbsp;Fernanda Tibolla Viero,&nbsp;Brenda da Silva,&nbsp;Gabriela Trevisan","doi":"10.1016/j.niox.2025.07.002","DOIUrl":"10.1016/j.niox.2025.07.002","url":null,"abstract":"<div><h3>Background</h3><div>Endometriosis causes pelvic pain, inflammation, and increased oxidative stress levels. To assist in the diagnosis of endometriosis and molecular mechanisms, we propose synthesize the studies that NO levels in different samples using a systematic review and metanalysis. We also evaluate NO levels in different stages of endometriosis.</div></div><div><h3>Material/methods</h3><div>The protocol was registered with PROSPERO (CRD42023397591). We searched for all articles published up to November 2023 that evaluated NO levels in patients with endometriosis compared to control patients. We used the Newcastle-Ottawa Scale (NOS) to estimate the quality of the articles and the risk of bias. Publication bias was assessed using the Egger test and Begg test.</div></div><div><h3>Results</h3><div>In this study, 5795 articles were found, after revision 14 studies with 666 control patients and 881 patients with endometriosis were included. NO levels in the combined analysis of all samples from endometriosis patients were increased compared to control patients. Patients with type III/IV endometriosis showed higher levels of NO compared to controls in peritoneal fluid and serum/plasma. The increase in NO levels in patients with type III/IV endometriosis has a high quality of evidence without publication bias.</div></div><div><h3>Conclusion</h3><div>Here we demonstrate the increase of NO in peritoneal fluid samples from endometriosis patients. Therefore, NO levels may be directly linked to the pathophysiology of endometriosis and can be involved in the severity of endometriosis and inflammatory mechanisms.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"158 ","pages":"Pages 106-115"},"PeriodicalIF":3.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Catestatin alleviates PASMC phenotypic switching-mediated pulmonary arterial remodeling in a rat model of MCT-induced pulmonary arterial hypertension by promoting endothelium-derived no synthesis","authors":"Zheyu Liu ,&nbsp;Bo Cui ,&nbsp;Hao Ju ,&nbsp;Tuantuan Tan ,&nbsp;Jinchun Wu ,&nbsp;Manqi Yang ,&nbsp;Saeed Kashkooli ,&nbsp;Mian Cheng ,&nbsp;Gang Wu ,&nbsp;Tao Liu","doi":"10.1016/j.niox.2025.07.001","DOIUrl":"10.1016/j.niox.2025.07.001","url":null,"abstract":"<div><h3>Background</h3><div>Enhancing the nitric oxide (NO) signaling pathway is an effective strategy for treating pulmonary arterial hypertension (PAH). Previous research has found that Catestatin (CST) exerts a negative inotropic effect by upregulating NO production. However, the effect of CST on PAH remains unclear.</div></div><div><h3>Methods</h3><div>In vivo, PAH was induced in rats by monocrotaline (MCT) injection. After MCT administration, continuous CST treatment was applied to the experimental group. At study conclusion, echocardiographic, hemodynamic, and histological assessments were performed. In vitro, the effects of CST on rat pulmonary arterial endothelial dysfunction and phenotypic switching of rat pulmonary arterial smooth muscle cells (rPASMC) under PAH-like conditions were investigated. The role of NO in rPASMC phenotypic switching was also explored.</div></div><div><h3>Results</h3><div>In vivo experiments demonstrated that CST significantly improved right heart structure and function in rats with PAH, reduced pulmonary arterial pressure, and alleviated remodeling of the right ventricle and pulmonary arteries. These effects were likely mediated by upregulation of the eNOS/cGMP/PKG pathway. In vitro, CST promoted endothelial NO synthesis via the PI3K/Akt/eNOS pathway, but had no significant impact on the proliferation or migration of rPASMCs. In contrast, exogenous NO effectively inhibited rPASMC phenotypic switching by arresting the cell cycle at the G0/G1 phase.</div></div><div><h3>Conclusion</h3><div>CST enhances endothelial NO synthesis through the PI3K/Akt/eNOS pathway, which subsequently acts on rPASMCs to inhibit their phenotypic switching via the NO/cGMP/PKG signaling pathway, thereby alleviating pulmonary arterial remodeling in PAH.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"158 ","pages":"Pages 93-105"},"PeriodicalIF":3.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIRT3 sulfhydrylation by hydrogen sulphide: A novel approach to prevent ferroptosis and atrial fibrosis","authors":"Zi-Zhu Zhang ,&nbsp;Xiu-Heng Wang ,&nbsp;Zhi-Hong Ning ,&nbsp;Yun Ou ,&nbsp;Jia-Yan Yang ,&nbsp;Hui-Fang Tang ,&nbsp;Zhi-Sheng Jiang ,&nbsp;Heng-Jing Hu","doi":"10.1016/j.niox.2025.06.006","DOIUrl":"10.1016/j.niox.2025.06.006","url":null,"abstract":"<div><h3>Background</h3><div>Hydrogen sulfide (H₂S) has been shown to counteract ferroptosis and atrial fibrosis, yet the underlying mechanisms remain incompletely understood. This study aims to investigate how H₂S regulates ferroptosis to alleviate atrial fibrosis.</div></div><div><h3>Methods</h3><div>In vivo and in vitro models of atrial fibrosis were established using Angiotensin II (Ang-II) to modulate the expression of SIRT3, β-catenin, and ferroptosis markers. Western blotting was employed to analyze changes in proteins related to ferroptosis and fibrosis. Histological evaluations, including Hematoxylin and Eosin (HE), and Masson's staining were performed to assess atrial fibrosis. Cardiac ultrasound was used to assess left atrial function in vivo. In vitro, reactive oxygen species (ROS) levels and iron staining were used to monitor ferroptosis and oxidative stress.</div></div><div><h3>Results</h3><div>In atrial tissue from patients with AF, significant increases in ferroptosis markers and atrial fibrosis were observed. In both animal and cell models of atrial fibrosis, reduced sulfhydrylated SIRT3 and elevated β-catenin expression were associated with increased ferroptosis and fibrosis markers. Treatment with NaHS, a donor of H₂S, reversed these changes, reducing both ferroptosis and fibrosis. Importantly, inhibition of sulfhydrylated SIRT3 further upregulated β-catenin, exacerbating ferroptosis and fibrosis. However, blocking β-catenin effectively alleviated Ang–II–induced ferroptosis and fibrosis in the atrial fibrosis model.</div></div><div><h3>Conclusion</h3><div>H₂S alleviates atrial fibrosis and inhibits ferroptosis by upregulating SIRT3 sulfhydrylation and antagonizing the Wnt/β-catenin signaling pathway. These findings suggest that targeting the H₂S-SIRT3-β-catenin signaling axis may offer a promising therapeutic strategy for atrial fibrosis and associated arrhythmias.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"158 ","pages":"Pages 82-92"},"PeriodicalIF":3.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inorganic nitrate stores, astrocyte metabolism and brain health: An emerging paradigm","authors":"Mario Siervo ,&nbsp;Giuseppe Verdile ,&nbsp;Barbora Piknova","doi":"10.1016/j.niox.2025.06.005","DOIUrl":"10.1016/j.niox.2025.06.005","url":null,"abstract":"<div><div>Inorganic nitrate plays a crucial role in the regulation of cerebral blood flow and neurotransmission through its conversion to nitric oxide (NO). Astrocytes are star-shaped glial cells and contribute to maintain the blood-brain barrier integrity, regulate neuronal metabolism, support synaptic plasticity and facilitate neurovascular coupling. Inorganic nitrate widely distributed through all organs, with main reservoirs in skeletomuscular and skin tissues. These reserves are easily accessible via bloodstream and processed into nitrite and NO mainly in liver. Processing nitrate/nitrite into NO at organ with main glycogen stores, could suggest an evolutionary coordination between energy metabolism and NO generating pathways. Such spatial arrangement may facilitate the synchronised mobilisation during periods of enhanced metabolic demand, optimising both fuel utilisation and vascular response and assuring optimal fuel distribution. Astrocytes store glycogen in the brain, which support neuronal metabolism during periods of increased neural activity and hypoglycaemia.</div><div>This review explores the hypothesis that inorganic nitrate may be stored alongside glycogen in astrocytes and serve as critical reserves for NO production in the brain, particularly during hypoxic conditions. We examine the emerging evidence that astrocytes serve as key mediators in this alternative nitrate-nitrite-NO pathway, potentially influencing cerebrovascular regulation, neuronal energetics, and cognitive function. The integration of findings across molecular, cellular, and systems neuroscience offers new perspectives on how inorganic nitrate intake might support brain metabolism and could inform both preventive strategies and therapeutic interventions for neuro-degenerative disorders such as age-related dementia, stroke or Parkinson's Disease.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"158 ","pages":"Pages 76-81"},"PeriodicalIF":3.2,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3-mercaptopyruvate sulfurtransferase resides on the inner mitochondrial membrane","authors":"Antonia Katsouda ,&nbsp;Eleni Vasilaki ,&nbsp;Markos Fountoulakis ,&nbsp;Ioanna Tremi ,&nbsp;Sophia Havaki ,&nbsp;Vassilios Myrianthopoulos ,&nbsp;Vassilis G. Gorgoulis ,&nbsp;Emmanuel Mikros ,&nbsp;Andreas Papapetropoulos","doi":"10.1016/j.niox.2025.06.004","DOIUrl":"10.1016/j.niox.2025.06.004","url":null,"abstract":"<div><div>3-mercaptopyruvate sulfurtransferase (MPST) is an enzyme implicated in the generation of the gasotransmitter hydrogen sulfide (H₂S). Unlike, the other two H₂S-synthesizing enzymes cystathionine gamma lyase (CSE) and cystathionine beta synthase (CBS), MPST is found in the mitochondria. However, the mechanisms through which MPST gains access to the mitochondria and its exact localization within this organelle remain unclear. Using immunogold electron microscopy staining, we localized MPST on the inner mitochondrial membrane. To study the pathway of mitochondrial entry for MPST, pharmacological inhibitors of different components of the translocase of outer/inner membrane were used. In line with the observation that ΜPST is found on the inner mitochondrial membrane, inhibition of TIM23 blocked MPST mitochondrial entry. Generation of N-terminally truncated forms of ΜPST did not interfere with the ability of the enzyme to gain access into the mitochondria, suggesting that an N-terminal pre-sequence does not mediate MPST mitochondrial entry. In agreement to this finding, cytosolic and mitochondrial MPST had a similar molecular weight. Interestingly, N-terminally deleted MPST exhibited reduced expression levels, indicating that this part of the enzyme is required for protein stability. Molecular dynamics simulations confirmed that deletion of the first 39 amino acids of the enzyme destabilizes the protein. Our findings reveal that MPST is present on the inner mitochondrial membrane and that its entry into mitochondria does not involve the N-terminus of the protein.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"158 ","pages":"Pages 67-75"},"PeriodicalIF":3.2,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Appearances can be deceiving: differences in FeNO values among COPD and severe asthmatic patients stratified according to peripheral eosinophilic count","authors":"Claudio Candia ,&nbsp;Silvestro Ennio D'Anna ,&nbsp;Maria D'Amato ,&nbsp;Francesco Cappello ,&nbsp;Andrea Motta ,&nbsp;Mauro Maniscalco","doi":"10.1016/j.niox.2025.06.003","DOIUrl":"10.1016/j.niox.2025.06.003","url":null,"abstract":"<div><div>Eosinophilic COPD (eCOPD) and eosinophilic severe asthma (eSA) appear to share relevant clinical features, including responsiveness to steroids and higher exacerbation rates. However, data on the expression of T2-high inflammation biomarkers and, in particular comparison of fractional exhaled nitric oxide (FeNO) levels between the two diseases is lacking. The aim of the current retrospective observational study was to investigate whether FeNO values might differ between eCOPD and eSA patients.</div><div>Sixty patients with SA and 40 with COPD were enrolled. They were divided in four groups: eosinophilic COPD (eCOPD) and eosinophilic severe asthma (eSA), if the blood eosinophil count (BEC) was ≥300 cells/μL; non-eosinophilic COPD (neCOPD) and non-eosinophilic severe asthma (neSA) if the BEC was &lt;100 cells/μL. FeNO values, lung function and demographic data were compared between the groups.</div><div>Overall, COPD patients were older, with a higher prevalence of males and had more impaired lung function than asthmatic patients. When comparing FeNO levels among the four groups, a significant difference was found between eCOPD and eSA patients (<em>p</em> = 0.001), as well as eCOPD and neCOPD patients (<em>p =</em> 0.021). Finally, neCOPD patients showed significantly lower FeNO values in comparison with neSA patients (<em>p =</em> 0.005). Such results were confirmed after adjusting for age, sex, and smoking history.</div><div>Our preliminary results hint at the possibility that, despite an apparently similar eosinophilic phenotype, eCOPD patients might present with different FeNO values in comparison with eSA patients, possibly reflecting different underlying disease mechanisms.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"158 ","pages":"Pages 62-66"},"PeriodicalIF":3.2,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of low nitrate/nitrite diet and nitrate supplementation on litter size and fetal and placental growth in pregnant mice","authors":"Hager M. Kowash ,&nbsp;Teresa Tropea ,&nbsp;Mark R. Dilworth ,&nbsp;Jon O. Lundberg ,&nbsp;Eddie Weitzberg ,&nbsp;Carina Nihlen ,&nbsp;Elizabeth C. Cottrell","doi":"10.1016/j.niox.2025.06.002","DOIUrl":"10.1016/j.niox.2025.06.002","url":null,"abstract":"<div><h3>Background</h3><div>In pregnancy, nitric oxide (NO) plays important roles in embryo development, maternal cardiovascular function, fetoplacental blood flow and fetal growth. Whilst the importance of NO synthase (NOS)-derived NO has been studied in pregnancy, evidence for the role of NO derived from dietary nitrate is lacking. Herein, we utilised dietary manipulation strategies to investigate the effects of dietary nitrate depletion/supplementation on pregnancy outcomes in mice.</div></div><div><h3>Methods</h3><div>Pregnant dams received either a standard control diet or a commercially available nitrate/nitrite depleted (low NOx) diet from the start of pregnancy, along with drinking water containing either 0.7 mM NaNO₃ or 0.7 mM NaCl as control. Pregnancy outcomes (litter size, fetal/placental weights) and maternal and fetal plasma nitrate/nitrite concentrations were determined at gestational day 17.5.</div></div><div><h3>Results and discussion</h3><div>Litter size was unaffected by maternal low NOx diet, but fetal and placental weights were significantly reduced (p &lt; 0.001 for both). Maternal plasma nitrate and nitrite concentrations were significantly lower in low NOx animals (p = 0.017 and p = 0.003, respectively), with maternal 0.7 mM NaNO₃ supplementation restoring nitrate, but not nitrite, levels. Whilst fetal and placental weights were unaffected by maternal NaNO₃ supplementation, litter size was significantly increased (p = 0.024). Unexpectedly, maternal food/energy intake was significantly reduced in low NOx dams (p &lt; 0.001), suggesting that the lower fetal and placental weights may be due to nutrient insufficiency, rather than nitrate depletion <em>per se</em>. These findings have important implications for the interpretation of studies using commercial low NOx diets to study the effects of nitrate-depletion, particularly where food intake has not been previously reported.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"158 ","pages":"Pages 45-51"},"PeriodicalIF":3.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}