{"title":"Divergent roles of endothelial and red blood cell nitric oxide synthase in regulating cardiovascular function during anemia","authors":"Vithya Yogathasan , Patricia Wischmann , Isabella Solga , Lilly Jäger , Stefanie Becher , Miriam M. Cortese-Krott , Norbert Gerdes , Malte Kelm , Christian Jung , Ramesh Chennupati","doi":"10.1016/j.niox.2025.08.004","DOIUrl":"10.1016/j.niox.2025.08.004","url":null,"abstract":"<div><h3>Background</h3><div>Red blood cells (RBCs) express functional endothelial nitric oxide synthase (eNOS), which regulates blood pressure (BP) independently of eNOS in endothelial cells (ECs) and provides cardioprotection during acute myocardial infarction (AMI). The functional role of RBC- and EC- eNOS in anemia remains unknown. This study evaluated the effects of RBC- or EC-specific eNOS deletion on hemodynamics and cardiac function in blood loss anemia.</div></div><div><h3>Methods</h3><div>and resultsAnemia was induced in EC- or RBC-specific eNOS knockout (KO) mice and their respective controls. In vivo flow-mediated dilation (FMD) was preserved in RBC-eNOS-KO mice under both baseline and anemic conditions but was impaired in EC-eNOS-KO mice compared to their respective controls. Wire myograph analysis of aortic rings showed preserved endothelium-dependent relaxation (EDR) in anemic RBC-eNOS-KO mice, while EDR was abolished in anemic EC-eNOS-KO mice relative to controls. Miller catheter BP measurements revealed elevated systolic and diastolic BP in EC-eNOS-KO mice under both baseline and anemic conditions. Both systolic and diastolic BP were increased in RBC-eNOS-KO mice compared to controls, whereas these parameters remained unchanged in anemic RBC-eNOS-KO mice compared to their respective controls. Echocardiography demonstrated preserved cardiac function across all genotypes at baseline, 3 days post-anemia, and 24 h post-reperfused AMI. However, infarct size was significantly increased in anemic RBC-eNOS-KO mice compared to controls.</div></div><div><h3>Conclusions</h3><div>Anemia mitigates the BP elevation caused by RBC-eNOS deletion, while hypertension persists in the absence of endothelial eNOS, highlighting vascular eNOS as the predominant regulator of BP under anemic conditions. RBC-eNOS limits infarct size under anemic conditions.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 1-10"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906965","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}
Joseph A. Bauer , Annette M. Sysel , Michael J. Dunphy
{"title":"A versatile vanadium(III)-based chemiluminescence protocol for nitric oxide metabolite quantification and NO release kinetics","authors":"Joseph A. Bauer , Annette M. Sysel , Michael J. Dunphy","doi":"10.1016/j.niox.2025.10.006","DOIUrl":"10.1016/j.niox.2025.10.006","url":null,"abstract":"<div><div>Nitric oxide (NO) is a central mediator of vascular, neurological, and immune functions, and its dysregulation is implicated in a broad spectrum of diseases. Despite its significance, direct measurement of NO in human samples is limited by its transient nature and rapid conversion to nitrate and nitrite. Accurate, rapid, and accessible quantification of these NO metabolites in clinical and research settings remains a key need. We present a vanadium(III)-based chemiluminescence protocol for the reliable detection of nitrate and nitrite in human biological fluids, including serum, urine, and cerebrospinal fluid. In addition, this method supports headspace gas analysis, enabling precise determination of nitric oxide release kinetics and half-life from NO-producing compounds. This approach offers a cost-effective and scalable solution suitable for routine analysis in both diagnostic and research laboratories.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 161-167"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252181","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}
Yuriy E. Kolupaev , Tetiana O. Yastreb , Alla Yemets , Yaroslav Blume
{"title":"Nitric oxide functional relationships with nitrogen-containing stress metabolites: Role in plant adaptation to adverse abiotic factors","authors":"Yuriy E. Kolupaev , Tetiana O. Yastreb , Alla Yemets , Yaroslav Blume","doi":"10.1016/j.niox.2025.10.003","DOIUrl":"10.1016/j.niox.2025.10.003","url":null,"abstract":"<div><div>Polyamines, γ-aminobutyric acid (GABA), proline, and glycine betaine (GB) are important plant stress metabolites that are interconnected in common metabolic cycles. These compounds have a multifunctional protective effect on plant cells under stress conditions, acting as osmoregulators, antioxidants, chaperones, and intracellular pH stabilizers, among other roles. The key role of these compounds, however, lies in their involvement in the signaling network of plant cells. Stress metabolites, in particular, engage in a complex functional interaction with reactive oxygen species (ROS) and nitric oxide (NO). Nevertheless, information detailing the links between NO and major nitrogen-containing stress metabolites is fragmented. Consequently, a holistic understanding of these interactions, even at the theoretical model level, has yet to be presented in the literature. The review investigates the phenomenology and mechanisms of NO's involvement as a signaling mediator in the stress-protective function of polyamines and GABA in plants. It also analyses the effect of NO on the content of polyamines, GABA, proline, and GB under normal and stressful conditions. The latest data on the role of S-nitrosation processes of enzymes involved in the regulation of content of low-molecular nitrogen-containing compounds in plant adaptation, and on the effect of polyamines on S-nitrosation of the proteome are summarized. Particular attention is paid to the links between nitric oxide and other signaling mediators (primarily ROS and Ca<sup>2+</sup>) during its functional interaction with stress metabolites. Regulation of NO and stress metabolite levels is considered one of the promising tools for managing plant stress resistance.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 126-146"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244823","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}
Brenda da Silva , Fernanda Tibolla Viero , Caren Tatiane de David Antoniazzi , Sabrina Qader Kudsi , Diulle Spat Peres , Ricardo Iuri Felix Morais , Leonardo Gomes Pereira , Gabriela Trevisan
{"title":"7-Nitroindazole, an nNOS inhibitor, reduces migraine-like nociception, demyelination, and anxiety-like behavior in a mouse model of relapsing-remitting multiple sclerosis","authors":"Brenda da Silva , Fernanda Tibolla Viero , Caren Tatiane de David Antoniazzi , Sabrina Qader Kudsi , Diulle Spat Peres , Ricardo Iuri Felix Morais , Leonardo Gomes Pereira , Gabriela Trevisan","doi":"10.1016/j.niox.2025.09.003","DOIUrl":"10.1016/j.niox.2025.09.003","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a complex neuroinflammatory disease often associated with migraine and anxiety, both of which impair quality of life. MS pathology involves intense inflammatory and oxidative processes, including increased nitric oxide (NO) production. However, the role of NO in MS-related migraine symptoms remains unclear. This study evaluated whether repeated administration of 7-nitroindazole (7-NI), a selective neuronal nitric oxide synthase (nNOS) inhibitor, could alleviate migraine-like nociception, anxiety-like behavior, and neuroinflammatory biomarkers in a relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE) mouse model. RR-EAE was induced in female C57BL/6 mice (20–30 g) using myelin oligodendrocyte glycoprotein (MOG35-55) and Quillaja saponin as an adjuvant. Mice received daily intragastric 7-NI (120 mg/kg) from day 20–35 post-induction. Disease progression, mechanical/spontaneous allodynia, and anxiety-like behavior were assessed. At the end of the protocol, oxidative and inflammatory biomarkers were analyzed. 7-NI treatment significantly reduced disease severity and nociception, exerted an anxiolytic effect, and improved myelin quality parameters. It inhibited the increase of oxidative and nitrosative markers (NOx, H<sub>2</sub>O<sub>2</sub>) in the brainstem, trigeminal ganglion, and plasma. Treatment also prevented plasma calcitonin gene-related peptide elevation and increased anti-inflammatory cytokines (IL-4, IL-10), suggesting positive modulation of neuroinflammation in RR-EAE. These findings highlight the therapeutic potential of 7-NI in MS; however, further studies are required to confirm its safety and efficacy in different populations and chronic disease contexts.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 51-62"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065441","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}
Dong Ding , Ran Tian , Xiao Yang , Zhe Ren , Zhi-Cheng Jing , Xin-Tong Wu , Lian-Wen Sun
{"title":"Corrigendum to “The impact of ciliary length on the mechanical response of osteocytes to fluid shear stress” [Nitric Oxide 155 2025 1–11]","authors":"Dong Ding , Ran Tian , Xiao Yang , Zhe Ren , Zhi-Cheng Jing , Xin-Tong Wu , Lian-Wen Sun","doi":"10.1016/j.niox.2025.09.001","DOIUrl":"10.1016/j.niox.2025.09.001","url":null,"abstract":"","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 38-39"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004508","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":"5-HT7 receptor antagonist SB269970 attenuates seizures by modulating NO/cGMP signaling pathway and neuroinflammation in a pentylenetetrazol-induced epilepsy model in rats","authors":"Handan Gunes, Ercan Ozdemir, Ahmet Sevki Taskiran","doi":"10.1016/j.niox.2025.09.006","DOIUrl":"10.1016/j.niox.2025.09.006","url":null,"abstract":"<div><div>Epilepsy is a disease affecting the quality of life, characterized by neuronal excessive discharges resulting from the disruption of the balance between excitatory and inhibitory systems in the brain, and its pathophysiology has not been fully elucidated. In this study, we investigated the effects of serotonin 7 (5-HT7) receptor antagonist SB 269970 on seizures in a pentylenetetrazol (PTZ)-induced epilepsy model. Seventy male Wistar Albino rats (weight 230–250 g) were used in the study and the rats were randomly assigned to control and drug groups. Predetermined doses of SB 269970 (3 mg/kg), 5-HT7 agonist AS 19 (5 mg/kg), 7-NI (nNOS inhibitor, 50 mg/kg), YC-1 (guanylate cyclase activator, 10 μg/kg) were administered to the rats. PTZ (35 mg/kg) was injected intraperitoneally to induce seizures. The Racine scale was used to evaluate seizure stages. After electrocorticography (ECoG) and video recordings, the rats were sacrificed and nitric oxide (NO), cGMP, nNOS and proinflammatory cytokines (TNF-α, IL-1β and IL-6) levels in hippocampal tissue were measured by biochemical methods. The study results showed that the seizure threshold increased and the number of seizures decreased in rats administered SB 269970. In addition, the levels of proinflammatory cytokines (TNF-α, IL-6, IL-1β) and NO, cGMP and nNOS, which are increased with seizures in the hippocampal tissue, were significantly decreased by the administration of SB 269970. In contrast, the administration of 5-HT7 agonist AS-19 increased the number of seizures and caused an increase in the levels of hippocampal proinflammatory cytokines and NO, cGMP and nNOS. In conclusion, the findings of this study revealed that SB 269970 causes anticonvulsant activity by inhibiting the NO/cGMP pathway and proinflammatory cytokine (TNF-α, IL-1β and IL-6) levels in the hippocampal tissue. However, further molecular studies are needed for 5-HT7 antagonist drugs to be an option in the treatment of epilepsy.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 78-88"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220300","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":"Roles of nitric oxide in improving post-harvest horticultural product quality: Crosstalk with hydrogen sulfide","authors":"Yali Qiao , Yayu Liu , Jihua Yu , Weibiao Liao","doi":"10.1016/j.niox.2025.10.004","DOIUrl":"10.1016/j.niox.2025.10.004","url":null,"abstract":"<div><div>Postharvest quality maintenance is a key research focus in horticultural science. Nitric oxide (NO), a vital gaseous signaling molecule, significantly improves postharvest quality by inhibiting ethylene (ETH) synthesis, reducing respiration rate, enhancing antioxidant enzyme systems, maintaining cell wall integrity, and regulating secondary metabolism. Currently, the synergistic mechanisms between NO and hydrogen sulfide (H<sub>2</sub>S) have emerged as a research hotspot. The two molecules work in concert to delay postharvest senescence and enhance fruit resistance to low temperature and pathogens involving enzyme activity regulation and physiological synergy. This review provides a comprehensive analysis of the independent regulatory effects of NO and its crosstalk mechanisms with H<sub>2</sub>S, providing theoretical foundations for developing efficient and safe postharvest preservation technologies and highlighting their potential applications in green preservation.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 102-114"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252167","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":"Diabetic nephropathy: Role of nitric oxide","authors":"Sajad Jeddi , Khosrow Kashfi , Asghar Ghasemi","doi":"10.1016/j.niox.2025.10.001","DOIUrl":"10.1016/j.niox.2025.10.001","url":null,"abstract":"<div><div>Diabetic nephropathy (DN) is characterized by structural kidney alterations—including glomerular basement membrane thickening, mesangial expansion, tubulointerstitial fibrosis, and glomerular hypertrophy—alongside functional impairments such as reduced glomerular filtration rate (GFR) and albuminuria. DN progresses through five stages: pre-nephropathy, silent, incipient, overt nephropathy, and end-stage kidney disease (ESKD). Dysregulation of the nitric oxide synthase (NOS) pathway—including neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS)—has been increasingly implicated in DN pathogenesis. Evidence from preclinical models using NOS inhibitors and knockout mice, combined with human studies that identify NOS gene polymorphisms, supports this association. In early stages, hyperglycemia elevates GFR, driven by increased NO production from all three NOS isoforms. As the disease progresses, reduced eNOS-derived NO and persistent iNOS overexpression contribute to structural damage and a decline in GFR. NO donors have been shown to prevent early hyperfiltration and attenuate the subsequent decrease in GFR and renal injury characteristic of overt nephropathy. Thus, NO signaling plays a dual role in DN progression and represents a promising target for therapeutic intervention.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 89-101"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244776","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":"Diabetic peripheral neuropathy: Role of nitric oxide","authors":"Zahra Bahadoran , Asghar Ghasemi","doi":"10.1016/j.niox.2025.10.002","DOIUrl":"10.1016/j.niox.2025.10.002","url":null,"abstract":"<div><div>Diabetic peripheral neuropathy (DPN) is one of the most prevalent long-term complications in type 1 (T1DM) and type 2 (T2DM) diabetes mellitus and is characterized by structural (microangiopathy, axonal atrophy, impaired myelination, and disrupted Schwann cell-axon interactions) and functional (impaired axonal transport and sensory and motor disorders) changes in neurons. Nitric oxide (NO) contributes to the development and progression of DPN as it has a role in the perfusion and electrophysiological functions of neurons. NO is essential for sustaining nerve conduction velocity (NCV) through modulation of Na<sup>+</sup>/K<sup>+</sup>-ATPase activity. Isoform-specific alterations in NO synthase (NOS) expression and activity occur during the development of DPN. Neural NOS (nNOS) generally exhibits consistent downregulation, especially in T2DM models, whereas inducible NOS (iNOS) tends to be upregulated in the T1DM model. NO has been proposed as a potential therapeutic agent for DPN because of its potent vasodilatory effects. NO-donating derivatives (e.g., NCX1404, PRG150) have demonstrated both symptomatic and disease-modifying effects in DPN. In conclusion, NO plays a role in the pathophysiology of DPN and is a therapeutic target for managing neuropathy in diabetes.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 147-160"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244786","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}
Laxman Poudel , Thilini Karunarathna , Stephen Baker , Elmira Alipour , Matthew R. Dent , Jesús Tejero , Mark T. Gladwin , Anthony W. DeMartino , Daniel B. Kim-Shapiro
{"title":"Role of hydrogen sulfide in catalyzing the formation of NO-ferroheme","authors":"Laxman Poudel , Thilini Karunarathna , Stephen Baker , Elmira Alipour , Matthew R. Dent , Jesús Tejero , Mark T. Gladwin , Anthony W. DeMartino , Daniel B. Kim-Shapiro","doi":"10.1016/j.niox.2025.09.002","DOIUrl":"10.1016/j.niox.2025.09.002","url":null,"abstract":"<div><div>We recently demonstrated a rapid reaction between labile ferric heme and nitric oxide (NO) in the presence of reduced glutathione (GSH) or other small thiols in a process called thiol-catalyzed reductive nitrosylation, yielding a novel signaling molecule, labile nitrosyl ferrous heme (NO-ferroheme), which we and others have shown can regulate vasodilation and platelet homeostasis. Red blood cells (RBCs) contain high concentrations of GSH, and NO can be generated in the RBC via nitrite reduction and/or RBC endothelial nitric oxide synthase (eNOS) so that NO-ferroheme could, in principle, be formed in the RBC. NO-ferroheme may also form in other cells and compartments, including in plasma, where another small and reactive thiol species, hydrogen sulfide (H<sub>2</sub>S/HS<sup>−</sup>), is also present and may catalyze NO-ferroheme formation akin to GSH. Here, we compare the reactivity of GSH and hydrogen sulfide with hemin in physiologically relevant media, including human serum albumin (HSA) and RBC membranes. Strikingly, hydrogen sulfide demonstrated a second-order rate constant over 10 times higher than GSH. We propose that the increased solubility of H<sub>2</sub>S vs GSH in lipophilic environments – where labile heme is most readily found – and the increased steric hindrance of the bulkier GSH account for the faster reaction kinetics observed with hydrogen sulfide. Our findings suggest that the hydrogen sulfide-catalyzed reductive nitrosylation reaction produces thionitrous acid (HSNO), which readily undergoes further reactions with excess hydrogen sulfide to form nitrosopersulfide (SSNO<sup>−</sup>) and polysulfides. These results suggest a common theme in thiol-catalyzed reductive nitrosylation of labile ferric heme that could play an important role in NO signaling.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 40-50"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008359","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}