Basic & Clinical Pharmacology & Toxicology最新文献

{"title":"The Role of Hydroxychloroquine in the Management of Rheumatic Disorders: A Comprehensive Review","authors":"Ilker Ates,&nbsp;Hilal Sahin,&nbsp;Lalu Muhammad Irham,&nbsp;Serkan Yilmaz,&nbsp;Sinan Suzen","doi":"10.1111/bcpt.70082","DOIUrl":"https://doi.org/10.1111/bcpt.70082","url":null,"abstract":"<p>A drug preferred for its antimalarial effect called hydroxychloroquine (HCQ) has long been used to manage and avoid malaria. Nevertheless, its exact mode of action is still unknown. HCQ works through a variety of strategies to influence distinct molecular and cellular pathways. Additionally, HCQ has been demonstrated to be an effective treatment for rheumatic conditions such as primary Sjögren's syndrome, rheumatoid arthritis, antiphospholipid syndrome and systemic lupus erythematosus. Despite being widely regarded as safe, HCQ has been known to cause adverse responses; thus, doctors should closely evaluate rheumatism patients before taking these medications. The current study aims to emphasize the potential side effects of treatment while supporting the clinical usage of HCQ for autoimmune disorders.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673201","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":"Huoxin Pill Ameliorates Atrial Fibrillation by Modulating Autonomic Nervous Balance and Electrical Conduction Heterogeneity: Insights From Systems Pharmacology and Experimental Validation","authors":"Mimi Huang,&nbsp;Lingli Wang,&nbsp;Zejun Xu,&nbsp;Chenxing Huang,&nbsp;Sisi He,&nbsp;Yiqiu Liao,&nbsp;Jiaxuan Li,&nbsp;Fei Qin,&nbsp;Yongjun Chen,&nbsp;Qiqi Zhang,&nbsp;Hongjun Yang,&nbsp;Dongyan Liu,&nbsp;Taiyi Wang","doi":"10.1111/bcpt.70079","DOIUrl":"https://doi.org/10.1111/bcpt.70079","url":null,"abstract":"<div>\u0000 \u0000 <p>Huoxin Pill (HXP), a traditional Chinese medicine for cardiovascular diseases, demonstrates clinically reported anti-atrial fibrillation (AF) effects, though its mechanisms remain unclear. To investigate these mechanisms, we established an acetylcholine-calcium chloride (ACh-CaCl₂)-induced AF model in rats divided into control, AF, HXP (HXP-L: 3.33; HXP-M: 10; HXP-H: 30 mg/kg) and verapamil (25 mg/kg) groups. Following daily modelling, treatments were administered via gavage from Days 4 to 10. Electrocardiography (ECG) subsequently assessed AF susceptibility while echocardiography evaluated cardiac function. Systems pharmacology predicted HXP's targets/pathways for AF amelioration, with heart rate variability (HRV) and nerve activity recording examining autonomic balance. Electrical mapping quantified activation time (AT), conduction velocity (CV), conduction dispersion and effective refractory period (ERP) in isolated hearts. Results demonstrated that the AF group exhibited increased AF incidence/duration and decreased left ventricular ejection fraction/fractional shortening (LVEF/LVFS). Systems pharmacology revealed significant enrichment in cardiovascular pathways (including AF), while HRV and nerve recording indicated autonomic imbalance. Isolated AF hearts showed prolonged AT, slowed CV, increased conduction dispersion and shortened ERP. HXP significantly ameliorated these alterations. In conclusion, these findings suggest that HXP improves ACh-CaCl₂-induced AF, potentially through modulating autonomic nervous balance and atrial electrical conduction heterogeneity.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673203","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":"Blood Pressure–Lowering Effects of Aldosterone Synthase Inhibitors—A Systematic Review","authors":"Anders Almskou Rasmussen,&nbsp;Ketil Lehm Nordestgaard,&nbsp;Ulf Simonsen,&nbsp;Niels Henrik Buus","doi":"10.1111/bcpt.70080","DOIUrl":"https://doi.org/10.1111/bcpt.70080","url":null,"abstract":"<p>Excess aldosterone production contributes to the development of hypertension and results in fibrosis with dysfunction of the heart, vasculature and kidneys. Consequently, new agents have been developed to reduce endogenous aldosterone synthesis. The primary objective of this systematic review is to describe the BP-lowering effects of aldosterone synthase inhibitors (ASIs) in hypertensive patients and, secondly, to describe their potential renal protective effects and possible influence on cortisol production and plasma potassium. We searched PubMed, Embase and ClinicalTrials.gov and included randomized controlled and clinical trials according to PICO using the review tool Covidence. Thirteen studies were included and all demonstrated BP reduction through ASI treatment. Among patients with apparent resistant hypertension, the placebo-corrected reductions in seated systolic BP were 11.0 mmHg for baxdrostat and 9.6 mmHg for lorundrostat. A significant suppression of cortisol production was found for LCI699 (osilodrostat) but not for baxdrostat, lorundrostat, BI 690517 (vicadrostat) or dexfadrostat. Studies on BI 690517 showed a reduction in urine–albumin–creatinine ratio, indicating renal protection. ASIs may increase potassium levels. We conclude that ASIs have promising BP-lowering effects with very limited effects on cortisol production and offer reno-protective effects in chronic kidney disease. Studies on hypertensive target organ damage and cardiovascular outcomes are, however, lacking.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673202","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":"Antioxidant, Antiinflammatory and Antiapoptotic Effects of Lycopene in Rats With Vancomycin-Induced Nephrotoxicity","authors":"Hülya Demirkapı Atik,&nbsp;Orkun Atik,&nbsp;Recep Aslan,&nbsp;Yavuz Osman Birdane,&nbsp;Abdullah Eryavuz","doi":"10.1111/bcpt.70084","DOIUrl":"https://doi.org/10.1111/bcpt.70084","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The most important side effect of vancomycin (Vanco) is nephrotoxicity (NPT). Lycopene (Lyco) has been reported to have anti-inflammatory and anti-apoptotic properties in addition to its antioxidant activity. The aim is to investigate the protective efficacy of Lyco against the NPT condition that limits the use of Vanco.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>A total of 48 rats were used in the study in six groups of eight rats each, namely, Corn Oil Control, Lyco 5, Lyco 10, Vanco, Vanco + Lyco 5 and Vanco + Lyco 10.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Vanco (400 mg/kg, intraperitoneal) administered for 7 days elevated serum BUN, creatinine, uric acid levels and renal lipid peroxidation while decreasing renal GSH and the activity of the antioxidant enzymes SOD, CAT and GPx. Vanco also increased the levels of inflammatory markers NF-κB, TNF-<i>α</i>, Bcl-3 and p38<i>α</i> MAPK activity. It decreased the level of AQP-1 and increased the level of NGAL. In addition, it activated apoptosis by decreasing Bcl-2 and Procas-3 expression levels while increasing apoptotic p53, Bax and Cyt-c expression levels. Lyco treatment at both doses (5 and 10 mg/kg, orally) ameliorated NPT by reducing oxidative stress, inflammation and apoptosis, while the higher dose was more effective.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The findings showed that Lyco attenuated Vanco-induced NPT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144672933","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":"Efficacy and Safety of Clopidogrel With and Without a Proton Pump Inhibitor: A Systematic Review and Meta-Analysis","authors":"Magnus A. B. Axelsson,&nbsp;Naldy Parodi López,&nbsp;Eva Wikström Jonsson,&nbsp;Susanna M. Wallerstedt","doi":"10.1111/bcpt.70087","DOIUrl":"https://doi.org/10.1111/bcpt.70087","url":null,"abstract":"<p>Classifications of drug interaction alerts regarding clopidogrel and a proton pump inhibitor (PPI) differ between knowledge resources. In this systematic review, Medline, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) applying PICO criteria: P = patients on clopidogrel; I = intervention: PPI (subgroup: [es]omeprazole); C = comparison: no PPI (C1) or a PPI other than (es)omeprazole (C2); O = outcomes, main: a composite of cardiovascular events (efficacy); also: overt gastrointestinal bleeding (safety). Fourteen RCTs fulfilled the PICO criteria, five without high risk of bias and with at least one clinical event per study arm. Regarding efficacy with or without a PPI, the pooled risk ratio (RR) and risk difference (RD) were 1.08 (95% confidence interval (CI) 0.78; 1.50) and 0.2 percentage points (95% CI −0.9; 1.2), respectively (four RCTs; 4341 patients [96% also used aspirin, 98% receiving I used (es)omeprazole]; moderate certainty evidence). Regarding safety, the RR and RD were 0.13 (95% CI 0.03; 0.59) and −0.7 percentage points (95% CI −1.1; −0.3), respectively (one RCT; 3761 patients; moderate certainty evidence). The available evidence did not allow conclusions regarding omeprazole versus pantoprazole. In conclusion, concurrent use of a PPI probably does not largely affect clopidogrel efficacy, but probably reduces the risk of overt gastrointestinal bleeding.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144672932","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":"Risk of Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis Associated With Mebendazole Use","authors":"Ida M. Heerfordt,&nbsp;Espen Jimenez-Solem,&nbsp;Magnus Middelboe,&nbsp;Rasmus Huan Olsen,&nbsp;Henrik Horwitz","doi":"10.1111/bcpt.70086","DOIUrl":"https://doi.org/10.1111/bcpt.70086","url":null,"abstract":"<p>Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but potentially fatal conditions, most often caused by adverse reactions to medication [<span>1</span>]. They are characterized by widespread skin necrosis and detachment of the epidermis [<span>1</span>]. The conditions are considered part of a disease spectrum, differentiated primarily by the extent of skin involvement [<span>1</span>]. It is accepted that the triggering medication is generally used within 3 months before symptom onset [<span>1</span>].</p><p>Mebendazole, a commonly used anthelmintic in both children and adults, has rarely been associated with SJS and TEN, primarily through isolated case series [<span>2</span>]. Mebendazole acts by binding to a subunit of helminthic tubulin, inhibiting microtubule formation and thereby disrupting essential cellular processes [<span>3</span>]. While patient labels for mebendazole cite occurrences of SJS and TEN as rare, listed as occurring in between 1 in 10 000 and 1 in 1000 treatments, the actual risk has not been quantified in large-scale, population-based studies [<span>2, 4-6</span>].</p><p>This study aimed to quantify the risk of developing SJS and TEN associated with mebendazole usage, to alleviate fears and improve the clinical basis for rational decision-making in prescribing.</p><p>This study employed a nationwide, population-based design using the Danish National Health Registries [<span>7</span>]. All Danish residents are systematically registered in the Danish Civil Registration System with a unique personal identification number, enabling precise linkage across health registries [<span>7</span>].</p><p>First, we established a cohort consisting of the entire Danish population from 1994 to 2025. Using the Danish National Prescription Register [<span>7</span>], we identified all individuals who redeemed at least one prescription for mebendazole (Anatomical Therapeutic Chemical (ATC) code P02CA01). The Danish National Patient Register was used to identify all cases of first-time diagnosis of erythema multiforme bullosum/SJS (International Classification of Diseases, 10th Revision (ICD-10) code L51.1) or TEN (ICD-10 code L51.2) during the same period. Patients assigned both diagnoses were included on equal terms with those assigned only one diagnosis. Based on this cohort, we calculated the absolute frequency of SJS/TEN following mebendazole use.</p><p>Second, we conducted a nested case–control study within the same cohort. All individuals with a first-time diagnosis of SJS or TEN were identified as cases. For each case, 100 controls were selected using risk set sampling, matched on age, sex and index date, based on data from the Danish Civil Registration System. Participants were required to have been residents in Denmark for at least 1 year prior to the index date. Mebendazole prescription retrieval was assessed for both cases and controls during two exposure windows: within 3 months and within 12 months b","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624671","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":"New Monitoring Recommendations for Digoxin During the Last Decade Are Associated With Decreased Serum Digoxin Concentrations in Patient Samples","authors":"Anders Larsson,&nbsp;Anna-Karin Hamberg,&nbsp;Jonathan Cedernaes,&nbsp;Pär Hallberg,&nbsp;Johanna Helmersson Karlqvist,&nbsp;Mathias Karlsson","doi":"10.1111/bcpt.70083","DOIUrl":"https://doi.org/10.1111/bcpt.70083","url":null,"abstract":"<p>Digoxin has long been used to manage atrial fibrillation and heart failure. While therapeutic drug monitoring (TDM) became available in the late 1960s, recent studies suggest increased mortality at serum levels &gt; 1.0 ng/mL, prompting reassessment of the traditionally accepted range (0.8–2.0 ng/mL). This study evaluated trends in digoxin concentrations from 2004 to 2024 to assess alignment with updated recommendations. We retrospectively analysed 37 489 routine digoxin measurements from Uppsala University Hospital (2004–2024), including patient age, sex, sampling date and digoxin levels. Analytical platforms changed from Abbott's Architect to Roche's Cobas Pro during the study period. Trends over time and sex differences were evaluated. Of the samples, 17 771 were from males (median age 77) and 19 718 from females (median age 83). Median digoxin concentrations were 0.9 nmol/L for males and 1.0 nmol/L for females. About 30% of samples exceeded 1.2 nmol/L. Digoxin concentrations decreased over time (Spearman R = −0.191, <i>p</i> &lt; 0.000001), particularly in higher values. Associations with age were modest. Serum digoxin levels have declined over the past two decades, reflecting evolving guidelines, though elevated levels remain common, highlighting the need for ongoing clinical-laboratory alignment.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624592","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":"Models of Endocrine-Disrupting Effects: Human Placental Steroidogenesis","authors":"Line Mathiesen,&nbsp;Dea Sandal,&nbsp;Ida Elise Moelgaard Hammer,&nbsp;Bjarne Styrishave,&nbsp;Lisbeth E. Knudsen","doi":"10.1111/bcpt.70073","DOIUrl":"https://doi.org/10.1111/bcpt.70073","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Endocrine disruption during pregnancy has gained increasing interest as epidemiological studies report associations of exposures and adverse effects on fetal growth, followed by effects on the growing child and ultimately in the adult. When studying endocrine disruption during pregnancy, the placental steroidogenesis is difficult to model, as the human placenta is unique in the pathway of cellular uptake of cholesterol, the high levels of progesterone production and the expression of aromatase. Models to test for endocrine disruption should respect species differences, with preference to human models for human risk assessment. Here, we present existing research of placental steroidogenesis and other placental hormones using human placental models: placental perfusion, placental explants, fragments, microsomes and vesicles, primary cell culture, stem cells, placenta on a chip and choriocarcinoma cell cultures: BeWo, HTR-8/SVneo, Jar, JEG-3 and ACH-3P. We conclude that there is a lack of research focused on placental steroidogenesis and the effects of endocrine-disrupting compounds. Advantages and limitations of existing models are discussed, and future directions suggested.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598271","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":"A Comprehensive Narrative Review of Protonitazene: Pharmacological Characteristics, Detection Techniques, and Toxicology","authors":"Jake Verbeek,&nbsp;David J. Brinkman","doi":"10.1111/bcpt.70078","DOIUrl":"https://doi.org/10.1111/bcpt.70078","url":null,"abstract":"<p>Protonitazene (PNZ) is a synthetic opioid emerging in Europe, Australia, North America and South America with a rapidly increasing number of intoxications. To describe PNZ's pharmacological characteristics, detection methods and the clinical presentation and management of PNZ intoxications, the PubMed database was searched for original articles in English concerning PNZ in any way. All articles were read and analysed completely for their suitability for inclusion, based on the article type, integrity and its description of PNZ pharmacology, toxicology and PNZ intoxications. Of the 21 articles resulting from the search, 16 articles were included. PNZ is a μ-opioid receptor agonist that induces opioid-like effects at subnanomolar concentrations at a much higher potency than morphine and fentanyl. 4′-Hydroxy-nitazene is a shared metabolite of most nitazenes and can be detected in urine for longer than most nitazenes, providing a way to detect nitazenes without knowing the parent nitazene. PNZ is detectable in whole blood, urine, bile, gastric contents and hair using several forms of mass spectrometry at subnanomolar concentrations but is not detectable in urine using traditional opioid test strips. More reports about monointoxications of PNZ and an appropriate public health response are necessary.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581987","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":"Coronary Microvascular Dysfunction in Ischaemic Heart Disease: Lessons From Large Animal Models","authors":"Oana Sorop,&nbsp;J. van de Wouw,&nbsp;Daphne Merkus,&nbsp;Dirk J. Duncker","doi":"10.1111/bcpt.70074","DOIUrl":"https://doi.org/10.1111/bcpt.70074","url":null,"abstract":"<p>The coronary microvasculature is principally responsible for matching coronary blood flow to myocardial demand of oxygen and nutrients. Short-term control of coronary blood flow is achieved via alterations in coronary microvascular tone, whereas long-term control of coronary flow also involves remodelling of the coronary microvasculature, including adjustments in vascular structure, diameter and density. In the past 50 years, considerable research efforts have been directed at understanding the functional and structural coronary microvascular adaptations involved in matching myocardial oxygen supply to demand, and how these mechanisms are affected by various diseases. In this review article, we will discuss our current understanding of the mechanisms underlying the regulation of coronary microvascular tone under healthy physiological conditions and in ischaemic heart disease. We will specifically discuss the role of microvascular dysfunction in obstructive and non-obstructive coronary artery disease, as studied in large animal models and confirmed in human studies. Future research should be directed at further unravelling the disease-specific mechanisms of coronary microvascular dysfunction in order to identify therapeutic targets to improve microvascular function in patients with ischaemic heart disease.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581986","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}