Basic & Clinical Pharmacology & Toxicology最新文献

{"title":"Montelukast Induces Depressive-Like Behaviour in ICR Young Mice Through Oxidative Stress and Inflammatory Response","authors":"Shalawate Ayijiang,&nbsp;Murezati Tiliwaerde,&nbsp;Yaqi Yang,&nbsp;Yanlin Li,&nbsp;Huan Gao,&nbsp;Jingyi Jia,&nbsp;Shen Wang,&nbsp;Qi Liu,&nbsp;Zengliang Jin","doi":"10.1111/bcpt.70033","DOIUrl":"https://doi.org/10.1111/bcpt.70033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In response to the US Food and Drug Administration's black box warning highlighting the neuropsychiatric risks associated with montelukast, the mechanisms underlying these psychiatric adverse effects, particularly depression in paediatric populations, have remained poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To address this, we examined whether montelukast induces depression-like behaviours in an animal model and investigated the potential mechanisms. Young ICR mice were administered montelukast continuously for 28 days, and depression-like behaviours were assessed using the open field test (OFT), tail suspension test (TST), and forced swim test (FST). Oxidative stress and inflammatory markers were analysed via RT-qPCR, biochemical assays and western blot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results revealed that 24 h post-montelukast administration, cysteinyl leukotriene receptor 1 and malondialdehyde (MDA) levels were significantly upregulated in the hippocampus, while glutathione (GSH), glutathione peroxidase 4 (GPx4), superoxide dismutase 2 (SOD2) and catalase (CAT) levels were downregulated. After 28 days of treatment, MDA levels remained elevated, and GSH, GPx4, SOD2 and CAT levels were further reduced. Additionally, hippocampal interleukin-1β and serum corticosterone levels were increased, whereas hippocampal glucocorticoid receptor expression was decreased.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings collectively demonstrate that montelukast induces depression-like behaviours in young ICR mice through mechanisms involving enhanced oxidative stress and inflammatory responses.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Retene's Tumour-Initiating Potential: Integrating Computational and Experimental Approaches","authors":"Francisco Carlos da Silva Junior,&nbsp;Thiago Pires Cláudio,&nbsp;Ricardo Luiz Cavalcanti de Albuquerque-Júnior,&nbsp;Silvia Regina Batistuzzo de Medeiros","doi":"10.1111/bcpt.70034","DOIUrl":"https://doi.org/10.1111/bcpt.70034","url":null,"abstract":"&lt;p&gt;Currently, the US Environmental Protection Agency (EPA) classifies 16 PAHs as priority pollutants, including seven carcinogenic compounds [&lt;span&gt;1&lt;/span&gt;]. Nevertheless, numerous nonlisted PAHs may also contribute to carcinogenic effects, including Benzo[&lt;i&gt;a&lt;/i&gt;]pyrene (B[&lt;i&gt;a&lt;/i&gt;]P) and dibenzo[&lt;i&gt;a,h&lt;/i&gt;]anthracene [&lt;span&gt;2&lt;/span&gt;]. Retene (RET, 1-methyl-7-isopropylphenanthrene) is a polycyclic aromatic hydrocarbon (PAH) primarily formed during the combustion of coniferous wood and is a significant component of atmospheric particulate matter from forest fires [&lt;span&gt;3, 4&lt;/span&gt;]. Metabolic and mechanistic studies suggest that RET induces genotoxicity and chromosomal alterations through oxidative stress [&lt;span&gt;3&lt;/span&gt;], raising concerns about its potential carcinogenicity. Although RET is structurally similar to well-known carcinogenic PAHs, its toxicological risks remain poorly investigated.&lt;/p&gt;&lt;p&gt;Structure–activity relationship (SAR) models and in vivo studies are widely used to predict toxicity and assess carcinogenic potential [&lt;span&gt;5&lt;/span&gt;]. PAHs are known to induce skin carcinogenesis via metabolic activation in dermal models [&lt;span&gt;6&lt;/span&gt;], highlighting the relevance of such approaches. Given the limited data on RET's carcinogenic effects, this study aims to evaluate its tumour-initiating potential using SAR predictions and an in vivo Swiss albino mouse model. To our knowledge, no previous studies have explored RET's involvement in carcinogenesis, and our findings could help clarify its underestimated toxicological impact.&lt;/p&gt;&lt;p&gt;According to Danish(Q)SAR calibrated for Syrian hamster embryo (SHE) cells (Table 1), RET, B[&lt;i&gt;a&lt;/i&gt;]P and DMBA showed positive results for malignant transformation. Furthermore, structural alerts of the type &lt;i&gt;genotoxic carcinogenicity&lt;/i&gt; were detected for all PAHs investigated using ToxTree (Table 1). Moreover, when organ-specific carcinogenicity was analysed using the ROSC-Pred calibrated for rodents, RET, B[&lt;i&gt;a&lt;/i&gt;]P and DMBA were predicted to induce tumours in different organs or tissues, such as skin, lung, liver, and kidney (Supporting Information S2).&lt;/p&gt;&lt;p&gt;The compounds RET, B[&lt;i&gt;a&lt;/i&gt;]P and DMBA did not induce changes in body weight (&lt;i&gt;F&lt;/i&gt;&lt;sub&gt;6,34&lt;/sub&gt; = 1.203, &lt;i&gt;p&lt;/i&gt; = 0.32) or increase mortality (&lt;i&gt;p&lt;/i&gt; &gt; 0.42) (Supporting Information S3). Water (&lt;i&gt;F&lt;/i&gt;&lt;sub&gt;15,90&lt;/sub&gt; = 1.428, &lt;i&gt;p&lt;/i&gt; = 0.15) and food intake (&lt;i&gt;F&lt;/i&gt;&lt;sub&gt;2,40&lt;/sub&gt; = 0.904, &lt;i&gt;p&lt;/i&gt; = 0.43) remained unchanged among the experimental groups (Supporting Information S3). After 16 weeks of chemical exposure (Figure 1A), the B[&lt;i&gt;a&lt;/i&gt;]P, RET 10 μM and 30 μM groups developed papules, fungiform nodules and isolated leukoplastic plaques. In contrast, the SC and RET 10 μM groups exhibited skin thickening, wrinkling, minor ulcers and scaly hyperkeratosis, likely resulting from continuous acetone application. The InL varied significantly among groups (&lt;i&gt;F&lt;/i&gt;&lt;sub&gt;6,34&lt;/sub&gt; = 8.601, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) (Figure 1B)","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Foetal Exposure to Phthalates and Endocrine Effects on the Leydig Cell","authors":"Sarah Philbert Nielsen,&nbsp;Line Mathiesen,&nbsp;Peter Møller","doi":"10.1111/bcpt.70035","DOIUrl":"https://doi.org/10.1111/bcpt.70035","url":null,"abstract":"<p>This review examines the association between early life exposure to phthalates in human males and Leydig cell endocrine function. A systematic search was performed in PubMed and EMBASE, identifying 17 studies for analysis. Association scores weighted for number of phthalates and subjects were calculated for luteinizing hormone (LH), testosterone, testosterone/LH ratio and insulin-like factor 3 (INSL3). The scores ranges from full consistency of positive (score = 1), through inconsistent (score = 0), to negative/inverse (score = −1) associations. LH and early life phthalate exposure showed a statistically significant weighted phthalate association score of 0.18. Testosterone showed largely null results, whereas testosterone/LH ratio showed a negative association, both not statistically significant. A rise in LH, and decrease of testosterone/LH ratio, indicates that early life phthalate exposure results in a demand for a larger LH stimulus to produce the same amount of testosterone, and perhaps a decreased function of the Leydig cells, that manifests with the onset of high testosterone production in puberty and adulthood. A statistically non-significant decrease in INSL3 with a weighted phthalate association score of −0.29 supports this finding. An early life phthalate exposure-induced decline in Leydig cell function could possibly impact the spermatogenesis and adult male fertility.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin Rescues Renal Mitochondria From Multiple Stressors–Induced Oxidative Stress","authors":"Saeed Alshahrani,&nbsp;Muhammad H. Sultan,&nbsp;Hina Rashid,&nbsp;Firoz Alam,&nbsp;Andleeb Khan,&nbsp;Mohammad Suhail Akhter,&nbsp;Derayat Qamri,&nbsp;Saba Beigh,&nbsp;Farhana Riyaz","doi":"10.1111/bcpt.70031","DOIUrl":"https://doi.org/10.1111/bcpt.70031","url":null,"abstract":"<div>\u0000 \u0000 <p>The renal system is a significant organ system vulnerable to stress due to its physiological function of toxin elimination. Exposure to a wide array of xenobiotics in humans causes deleterious effects in the kidneys. In the present study, we observed the toxic effect of a coexposure of bisphenol A and acetaminophen on the renal function and renal mitochondria of Wistar rats and its amelioration by melatonin. The animals were grouped and treated for 4 weeks as follows: (I) control; (II) melatonin; (III) bisphenol A; (IV) acetaminophen; (V) bisphenol A and acetaminophen; and (VI) bisphenol A, acetaminophen and melatonin. Coadministration of bisphenol A and acetaminophen exposure significantly impaired renal function, elevating creatinine (2.28 mg/dL), BUN (65.42 mg/dL) and uric acid (6.11 mg/dL), while increasing oxidative stress and inflammatory markers (CAT: 3.85-μmol H₂O₂/min/mg protein, GPx: 189.57-nmol NADPH/min/mg protein, GR: 96.62-nmol NADPH/min/mg protein, MnSOD: 107.24-nmol (−) epinephrine/min/mg protein, IL-6: 1750 pg/mL, TNFα: 1677 pg/mL). Melatonin coadministration improved renal markers (creatinine: 1.60 mg/dL, BUN: 45.59 mg/dL, uric acid: 4.61 mg/dL) and partially restored antioxidant defences and inflammatory markers (CAT: 5.74-μmol H₂O₂/min/mg protein, GPx: 422.74-nmol NADPH/min/mg protein, GR: 136.91-nmol NADPH/min/mg protein, MnSOD: nmol (−) epinephrine prevented from oxidation/min/mg protein, IL-6: 1677 pg/mL, TNFα: 900 pg/mL). These findings suggest that melatonin mitigates bisphenol A and acetaminophen-induced renal damage by enhancing antioxidant defences and reducing inflammation.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Intraoperative Dexmedetomidine on Early Attention Network Function After Gynaecological Surgery: A Randomized Controlled Study","authors":"Chen Chen,&nbsp;Yinyao Feng,&nbsp;Weixiang Tang,&nbsp;Weiwei Zhong,&nbsp;Weiwei Wu,&nbsp;Guanghong Xu,&nbsp;Hu Liu","doi":"10.1111/bcpt.70032","DOIUrl":"https://doi.org/10.1111/bcpt.70032","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Perioperative neurocognitive disorder (PND) is a common neurological complication in patients after surgery and anaesthesia. Whether dexmedetomidine affects postoperative attention network function remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eighty patients aged 40–60 years underwent elective gynaecological surgery under total intravenous anaesthesia, before induction dexmedetomidine (group D) or placebo (group P) was used. The attention network test was used to assess the function of three attention networks pre- and post-operation, and blood samples were collected to test inflammatory factors and neurotransmitters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The three networks of the two groups were obviously impaired after the operation. Horizontally, on the 1st postoperative day, the degree of impairment of the alerting network in group D was less than that in group P (<i>p</i> = 0.033), and the orienting network was completely protected (<i>p</i> &lt; 0.001, vs. group P; <i>p</i> = 0.058, vs. baseline), while the executive control network improved (<i>p</i> &lt; 0.001, vs. group P; <i>p</i> = 0.045, vs. baseline). Moreover, all the inflammatory factors levels in group P increased on the 1st postoperative day. In contrast, the acetylcholine (ACh) and dopamine (DA) levels decreased significantly (<i>p</i> = 0.049 for ACh, <i>p</i> &lt; 0.001 for DA). In group D, the inflammatory factors and serum neurotransmitters showed different patterns.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Dexmedetomidine can protect against impairment of early postoperative attention network function in middle-aged female patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Registration Number</h3>\u0000 \u0000 <p>This trial has been registered with the Chinese Clinical Trial Registry (https://www.chictr.org.cn) (ChiCTR2000031283).</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Inflammatory and Proresolving Mediators in Endothelial Dysfunction","authors":"Ana M. Briones,&nbsp;Raquel Hernanz,&nbsp;Ana B. García-Redondo,&nbsp;Cristina Rodríguez,&nbsp;Luis M. Blanco-Colio,&nbsp;Almudena Val-Blasco,&nbsp;María J. Alonso,&nbsp;Mercedes Salaices","doi":"10.1111/bcpt.70026","DOIUrl":"https://doi.org/10.1111/bcpt.70026","url":null,"abstract":"<p>Excessive local inflammation is a common mechanism in many cardiovascular diseases (CVDs) such as hypertension, atherosclerosis and aortic aneurysms. In endothelial cells, inflammatory cytokines such as interferons, tumour necrosis factor alpha or interleukins increase oxidative stress and contractile prostanoids and the expression of adhesion molecules that reduce nitric oxide (NO) availability and bind leucocytes, thereby impairing endothelial function. Despite this evidence, anti-inflammatory therapies are not yet indicated for the treatment of most CVD. Resolution of inflammation is mediated by a family of specialized pro-resolving mediators (SPMs) that act on cognate G protein–coupled receptors to limit immune cell infiltration and initiate tissue repair. SPMs, generated from omega-3 and omega-6 polyunsaturated fatty acids, belong to four major families: lipoxins, resolvins, protectins and maresins. SPM receptors are expressed in immune and vascular cells where they regulate important processes such as phagocytosis and polarization, production of cytokines, NO and prostacyclin, and modulation of smooth muscle cell phenotype. Growing evidence in animal models demonstrates that activation of SPM receptors can protect vascular function and structure and provide beneficial effects in various CVD. We will review recent advances in the role of inflammation and SPMs in vascular (dys)function in hypertension, atherosclerosis, and aortic aneurysms.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pericyte Electrical Signalling and Brain Haemodynamics","authors":"Thomas A. Longden,&nbsp;Dominic Isaacs","doi":"10.1111/bcpt.70030","DOIUrl":"https://doi.org/10.1111/bcpt.70030","url":null,"abstract":"<p>Dynamic control of membrane potential lies at the nexus of a wide spectrum of biological processes, ranging from the control of individual cell secretions to the orchestration of complex thought and behaviour. Electrical signals in all vascular cell types (smooth muscle cells, endothelial cells and pericytes) contribute to the control of haemodynamics and energy delivery across spatiotemporal scales and throughout all tissues. Here, our goal is to review and synthesize key studies of electrical signalling within the brain vasculature and integrate these with recent data illustrating an important electrical signalling role for pericytes, in doing so attempting to work towards a holistic description of blood flow control in the brain by vascular electrical signalling. We use this as a framework for generating further questions that we believe are important to pursue. Drawing parallels with electrical signal integration in the nervous system may facilitate deeper insights into how signalling is organized within the vasculature and how it controls blood flow at the network level.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bruceine A Inhibits Cell Proliferation by Targeting the USP13/PARP1 Signalling Pathway in Multiple Myeloma","authors":"Mengjie Guo,&nbsp;Han Meng,&nbsp;Yi Sun,&nbsp;Lianxin Zhou,&nbsp;Tingting Hu,&nbsp;Tianyi Yu,&nbsp;Haowen Bai,&nbsp;Yuanjiao Zhang,&nbsp;Chunyan Gu,&nbsp;Ye Yang","doi":"10.1111/bcpt.70027","DOIUrl":"https://doi.org/10.1111/bcpt.70027","url":null,"abstract":"<p>Multiple myeloma (MM) is an incurable hematologic malignancy, driving significant interest in the discovery of novel therapeutic strategies. Bruceine A (BA), a tetracyclic triterpene quassinoid derived from <i>Brucea javanica</i>, has shown anticancer properties by modulating multiple intracellular signalling pathways and exhibiting various biological effects. However, the specific pharmacological mechanisms by which it combats MM remain unclear. In this study, we identified USP13 as a potential target of BA. We observed a significant increase in USP13 expression in patients with MM, which was strongly associated with a poorer prognosis. Furthermore, enhanced USP13 expression can stimulate MM cell proliferation both in vitro and in vivo. Mass spectrometry analysis, combined with co-immunoprecipitation and in vitro ubiquitination experiments, revealed PARP1 as a critical downstream target of USP13. USP13 can stabilize PARP1 protein through deubiquitination, promoting PARP1-mediated DNA damage repair (DDR) and facilitating MM progression. Notably, we utilized MM cell lines, an MM Patient-Derived Tumour Xenograft model, and a 5TMM3VT mouse model to determine the anticancer effects of BA on MM progression, revealing its potential to target USP13/PARP1 signalling and disrupt DDR in MM cells. In conclusion, these findings suggest that BA inhibiting USP13/PARP1-mediated DDR might be a promising therapeutic strategy for MM.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Cells of the Vasculature: Advances in the Regulation of Vascular Tone in the Brain and Periphery","authors":"Luke S. Dunaway,&nbsp;William A. Mills III,&nbsp;Ukpong B. Eyo,&nbsp;Brant E. Isakson","doi":"10.1111/bcpt.70023","DOIUrl":"https://doi.org/10.1111/bcpt.70023","url":null,"abstract":"<p>The vasculature is a complex tissue in which multiple cell types coordinate the regulation of tissue perfusion in response to hemodynamic and biochemical signals. Advances in this field are continuing to deepen our understanding of the relative importance of these cell types through the body. In the peripheral vasculature, tone is generated primarily by smooth muscle cells and regulated by endothelial cells, and neurons. In the brain parenchyma, unique cell types including pericytes, perivascular astrocytes and microglia, also contribute to the regulation of arterial and capillary tone. Here, we provide a cell-by-cell review of the regulation of vascular tone and highlight recent advances in the regulation of vascular tone in both the periphery and cerebral vasculature.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Ever-Expanding Influence of the Endothelial Nitric Oxide Synthase","authors":"Riham Rafea,&nbsp;Mauro Siragusa,&nbsp;Ingrid Fleming","doi":"10.1111/bcpt.70029","DOIUrl":"https://doi.org/10.1111/bcpt.70029","url":null,"abstract":"<p>Nitric oxide (NO) generated by the endothelial NO synthase (eNOS) plays an essential role in the maintenance of vascular homeostasis and the prevention of vascular inflammation. There are a myriad of mechanisms that regulate the activity of the enzyme that may prove to represent interesting therapeutic opportunities. In this regard, the kinases that phosphorylate the enzyme and regulate its activity in situations linked to vascular disease seem to be particularly promising. Although the actions of NO were initially linked mainly to the activation of the guanylyl cyclase and the generation of cyclic GMP in vascular smooth muscle cells and platelets, it is now clear that NO elicits the majority of its actions via its ability to modify redox-activated cysteine residues in a process referred to as <i>S</i>-nitrosylation. The more wide spread use of mass spectrometry to detect <i>S</i>-nitrosylated proteins has helped to identify just how large the NO sphere of influence is and just how many cellular processes are affected. It may be an old target, but the sheer impact of eNOS on vascular health really justifies a revaluation of therapeutic options to maintain and protect its activity in situations associated with a high risk of developing cardiovascular disease.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}