Vascular pharmacology最新文献

{"title":"Different gene expression patterns between mouse and human brain pericytes revealed by single-cell/nucleus RNA sequencing","authors":"Yuyang Miao ,&nbsp;Weihan Li ,&nbsp;Marie Jeansson ,&nbsp;Maarja Andaloussi Mäe ,&nbsp;Lars Muhl ,&nbsp;Liqun He","doi":"10.1016/j.vph.2024.107434","DOIUrl":"10.1016/j.vph.2024.107434","url":null,"abstract":"<div><h3>Aims</h3><div>Pericytes in the brain play important roles for microvascular physiology and pathology and are affected in neurological disorders and neurodegenerative diseases. Mouse models are often utilized for pathophysiology studies of the role of pericytes in disease; however, the translatability is unclear as brain pericytes from mouse and human have not been systematically compared. In this study, we investigate the similarities and differences of brain pericyte gene expression between mouse and human. Our analysis provides a comprehensive resource for translational studies of brain pericytes.</div></div><div><h3>Methods</h3><div>We integrated and compared four mouse and human adult brain pericyte single-cell/nucleus RNA-sequencing datasets derived using two single-cell RNA sequencing platforms: Smart-seq and 10x. Gene expression abundance and specificity were analyzed. Pericyte-specific/enriched genes were assigned by comparison with endothelial cells present in the same datasets, and mouse and human pericyte transcriptomes were subsequently compared to identify species-specific genes.</div></div><div><h3>Results</h3><div>An overall concordance between pericyte transcriptomes was found in both Smart-seq and 10x data. 206 orthologous genes were consistently differentially expressed between human and mouse from both platforms, 91 genes were specific/up-regulated in human and 115 in mouse. Gene ontology analysis revealed differences in transporter categories in mouse and human brain pericytes. Importantly, several genes implicated in human disease were expressed in human but not in mouse brain pericytes, including <em>SLC6A1</em>, <em>CACNA2D3</em>, and <em>SLC20A2</em>.</div></div><div><h3>Conclusions</h3><div>This study provides a systematic illustration of the similarities and differences between mouse and human adult brain pericytes.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"157 ","pages":"Article 107434"},"PeriodicalIF":3.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examining the controversies in venous thromboembolism prophylaxis for vascular surgery patients: A critical review","authors":"Tao Fang,&nbsp;Ran Zhang,&nbsp;Yanmei Li","doi":"10.1016/j.vph.2024.107436","DOIUrl":"10.1016/j.vph.2024.107436","url":null,"abstract":"<div><h3>Background</h3><div>Venous thromboembolism (VTE) is a significant concern in vascular surgery due to its potentially severe consequences. Effective prophylactic measures are essential to minimize the risks associated with VTE. However, considerable controversy remains regarding the optimal strategies for VTE prevention in patients undergoing vascular procedures.</div></div><div><h3>Methods</h3><div>This review critically analyzes key clinical research, guidelines, and expert opinions to explore the advantages and limitations of various VTE prophylaxis approaches. The pharmacological and mechanical methods are explored, with a focus on balancing the risk of VTE against the potential for bleeding complications, particularly in high-risk patients.</div></div><div><h3>Results</h3><div>The review addresses controversial issues such as the choice of anticoagulants, dosage, timing, and duration of prophylaxis. The lack of consensus in existing guidelines and the variability in clinical practice regarding VTE prevention in vascular surgery patients is highlighted. The role of patient-specific risk factors, including the use of intraoperative anticoagulation and bleeding risks, is also examined.</div></div><div><h3>Conclusion</h3><div>This review provides a comprehensive evaluation of VTE prophylaxis strategies in vascular surgery, emphasizing the need for individualized, evidence-based approaches. Clarifying these controversies is crucial for optimizing patient outcomes and minimizing both thrombotic and hemorrhagic complications.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"157 ","pages":"Article 107436"},"PeriodicalIF":3.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive lipids improve serum HDL and PON1 activities in coronary artery disease patients: Ex-vivo study","authors":"Ali Khattib ,&nbsp;Manar Shmet ,&nbsp;Achinoam Levi ,&nbsp;Tony Hayek ,&nbsp;Majdi Halabi ,&nbsp;Soliman Khatib","doi":"10.1016/j.vph.2024.107435","DOIUrl":"10.1016/j.vph.2024.107435","url":null,"abstract":"<div><h3>Background</h3><div>Atherosclerotic cardiovascular disease (CVD) remains a leading cause of vascular disease worldwide. Atherosclerosis is characterized by the accumulation of lipids and oxidized lipids on the blood vessel walls. Coronary artery disease (CAD) is the most common display of atherosclerotic CVD.</div></div><div><h3>Objectives</h3><div>We investigated the effects of the bioactive lipids as lyso-diacylglyceryltrimethylhomoserine (lyso-DGTS (20,5,0)) and its derivative oleoyl-<em>N</em>-trimethyl homoserine amide (oleoyl amide-MHS) on the properties and functionality of HDL and paraoxonase 1 (PON1) activities in the serum of individuals who exhibited arterial plaque as observed by coronary CT angiography (CCTA).</div></div><div><h3>Methods</h3><div>The study included two independent groups comprising 40 patients who had undergone arterial CCTA scans at Ziv Medical Center for various medical indications. The CAD group included 20 patients with coronary artery plaques with luminal stenosis of more than 50 % in a major coronary vessel. The control group consisted of 20 healthy patients (patients without artery plaques).</div></div><div><h3>Results</h3><div>Serum samples from CAD patients exhibited lower serum PON1 and cholesterol efflux activities and higher pro-inflammatory than the control group. HDL isolated from CAD patients contains elevated levels of oxidizing lipids (specifically lyso- phosphatidyl ethanolamines and lyso-phosphocholines(compared to the control. However, incubation of the CAD patients' serum with lyso-DGTS and oleoyl amide-MHS restored the antiatherogenic activities of HDL. The lipids increased serum PON1 activities, enhanced apoB-depleted serum cholesterol-efflux activity, and elevated the serum's anti-inflammatory properties.</div></div><div><h3>Conclusions</h3><div>The results of the present study suggest the potential of the bioactive lipids lyso-DGTS and oleoyl amide-MHS to attenuate atherosclerosis via the improvement of dysfunctional HDL properties and PON1 activities. Further, in-vivo experiments are needed to assess the athero-protective effect of the lipids.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"157 ","pages":"Article 107435"},"PeriodicalIF":3.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered copper transport in oxidative stress-dependent brain endothelial barrier dysfunction associated with Alzheimer's disease","authors":"Md. Selim Hossain ,&nbsp;Archita Das ,&nbsp;Ashiq M. Rafiq ,&nbsp;Ferenc Deák ,&nbsp;Zsolt Bagi ,&nbsp;Rashelle Outlaw ,&nbsp;Varadarajan Sudhahar ,&nbsp;Mai Yamamoto ,&nbsp;Jack H. Kaplan ,&nbsp;Masuko Ushio-Fukai ,&nbsp;Tohru Fukai","doi":"10.1016/j.vph.2024.107433","DOIUrl":"10.1016/j.vph.2024.107433","url":null,"abstract":"<div><div>Oxidative stress and blood-brain barrier (BBB) disruption due to brain endothelial barrier dysfunction contribute to Alzheimer's Disease (AD), which is characterized by beta-amyloid (Aβ) accumulation in senile plaques. Copper (Cu) is implicated in AD pathology and its levels are tightly controlled by several Cu transport proteins. However, their expression and role in AD, particularly in relation to brain endothelial barrier function remains unclear. In this study, we examined the expression of Cu transport proteins in the brains of AD mouse models as well as their involvement in Aβ42-induced brain endothelial barrier dysfunction. We found that the Cu uptake transporter CTR1 was upregulated, while the Cu exporter ATP7A was downregulated in the hippocampus of AD mouse models and in Aβ42-treated human brain microvascular endothelial cells (hBMECs). In the 5xFAD AD mouse model, Cu levels (assessed by ICP-MS) were elevated in the hippocampus. Moreover, in cultured hBMECs, Aβ42-induced reactive oxygen species (ROS) production, ROS-dependent loss in barrier function (measured by transendothelial electrical resistance), and tyrosine phosphorylation of CDH5 were all inhibited by either a membrane permeable Cu chelator or by knocking down CTR1 expression. These findings suggest that dysregulated expression of Cu transport proteins may lead to intracellular Cu accumulation in the AD brain, and that Aβ42 promotes ROS-dependent brain endothelial barrier dysfunction and CDH5 phosphorylation in a CTR1-Cu-dependent manner. Our study uncovers the critical role of Cu transport proteins in oxidative stress-related loss of BBB integrity in AD.</div></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"157 ","pages":"Article 107433"},"PeriodicalIF":3.5,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gaps in evidence in the treatment of prevalent patients with pulmonary arterial hypertension at intermediate risk: An expert consensus","authors":"Giovanna Manzi ,&nbsp;Raymond L. Benza ,&nbsp;Paola Argiento ,&nbsp;Gavino Casu ,&nbsp;Marco Corda ,&nbsp;Michele Correale ,&nbsp;Michele D'Alto ,&nbsp;Giuseppe Galgano ,&nbsp;Andrea Garascia ,&nbsp;Stefano Ghio ,&nbsp;Mardi Gomberg-Maitland ,&nbsp;Massimiliano Mulé ,&nbsp;Giuseppe Paciocco ,&nbsp;Silvia Papa ,&nbsp;Daniele Prati ,&nbsp;Ioana R. Preston ,&nbsp;Claudia Raineri ,&nbsp;Emanuele Romeo ,&nbsp;Laura Scelsi ,&nbsp;Davide Stolfo ,&nbsp;Carmine Dario Vizza","doi":"10.1016/j.vph.2024.107432","DOIUrl":"10.1016/j.vph.2024.107432","url":null,"abstract":"<div><p>Despite the innovations introduced in the 2022 European Society of Cardiology/European Respiratory Society Guidelines on Pulmonary Hypertension, risk discrimination and management of pulmonary arterial hypertension (PAH) patients at intermediate risk still represents a grey zone. Additionally, clinical evidence derived from currently available studies is limited. This expert panel survey intends to aid physicians in choosing the best therapeutic strategy for patients at intermediate risk despite ongoing oral therapy. An expert panel of 24 physicians, specialized in cardiology and/or pulmonology with expertise in handling all drugs available for the treatment of PAH participated in the survey. All potential therapeutic options for patients at intermediate risk were explored and analyzed to produce graded consensus statements regarding: the switch from endothelin receptor antagonist (ERA) or phosphodiesterase 5 inhibitor (PDE5i) to another oral drug of the same class; the addition of a drug targeting the prostacyclin pathway administered by different routes; the switch from PDE5i to riociguat.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"157 ","pages":"Article 107432"},"PeriodicalIF":3.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrix metalloproteinases in aortic dissection","authors":"Shufen Zhou ,&nbsp;Baihui Ma ,&nbsp;Mingyao Luo","doi":"10.1016/j.vph.2024.107420","DOIUrl":"10.1016/j.vph.2024.107420","url":null,"abstract":"<div><p>Aortic dissection, characterized by a high immediate mortality, is primarily caused by excessive bleeding within the walls of the aorta or a severe tear within the intimal layer of the aorta. Inflammation, as well as oxidative stress and the degradation of extracellular matrix (ECM), are significant factors in the development and occurrence of aortic dissection. Matrix metalloproteinases (MMPs) are pivotal enzymes responsible for degrading the ECM. Inflammatory factors and oxidants can interact with MMPs, indicating the potential significance of MMPs in aortic dissection. A substantial body of evidence indicates that numerous MMPs are significantly upregulated in aortic dissection, playing a critical role in ECM degradation and the pathogenesis of aortic dissection. Furthermore, targeting these enzymes has demonstrated potential in facilitating ECM restoration and reducing the incidence of aortic dissection. This review initially provides a brief overview of MMP biology before delving into their expression patterns, regulatory mechanisms, and therapeutic applications in aortic dissection. A profound comprehension of the catabolic pathways associated with aortic dissection is imperative for the future development of potential preventive or therapeutic bio-interventions for aortic dissection.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"156 ","pages":"Article 107420"},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in serum response factor posttranslational modifications and their therapeutic potential in cardiovascular and neurological diseases","authors":"Alexander Visconti ,&nbsp;Hongyu Qiu","doi":"10.1016/j.vph.2024.107421","DOIUrl":"10.1016/j.vph.2024.107421","url":null,"abstract":"<div><p>Serum Response Factor (SRF) is a key regulatory transcription factor present in various cell types throughout the body, playing essential roles in cellular functions under physiological conditions. Mutations and abnormal expression of SRF have been linked to the development of various diseases and disorders. Recent evidence highlights that post-translational modifications (PTMs) are critical for regulating SRF function in different cell types and contribute to disease pathogenesis. Targeting SRF-related PTMs is emerging as a promising therapeutic approach for treating SRF-associated diseases. In this review, we summarize recent advances in understanding SRF PTMs and their underlying regulatory mechanisms. We also explore the implications of SRF-PTM in related cardiovascular and neurological diseases and their potential for therapeutic intervention. This information underscores the significance of SRF PTMs in both physiological and pathological contexts, enhancing our understanding of disease mechanisms and paving the way for the development of novel therapeutic strategies.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"156 ","pages":"Article 107421"},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142098174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophages in vascular disease: Roles of mitochondria and metabolic mechanisms","authors":"Cameron D.A. Mackay ,&nbsp;Megan B. Meechem ,&nbsp;Vaibhav B. Patel","doi":"10.1016/j.vph.2024.107419","DOIUrl":"10.1016/j.vph.2024.107419","url":null,"abstract":"<div><p>Macrophages are a dynamic cell type of the immune system implicated in the pathophysiology of vascular diseases and are a major contributor to pathological inflammation. Excessive macrophage accumulation, activation, and polarization is observed in aortic aneurysm (AA), atherosclerosis, and pulmonary arterial hypertension. In general, macrophages become activated and polarized to a pro-inflammatory phenotype, which dramatically changes cell behavior to become pro-inflammatory and infiltrative. These cell types become cumbersome and fail to be cleared by normal mechanisms such as autophagy. The result is a hyper-inflammatory environment causing the recruitment of adjacent cells and circulating immune cells to further augment the inflammatory response. In AA, this leads to excessive ECM degradation and chemokine secretion, ultimately causing macrophages to dominate the immune cell landscape in the aortic wall. In atherosclerosis, monocytes are recruited to the vascular wall, where they polarize to the pro-inflammatory phenotype and induce inflammatory pathway activation. This leads to the development of foam cells, which significantly contribute to neointima and necrotic core formation in atherosclerotic plaques. Pro-inflammatory macrophages, which affect other vascular diseases, present with fragmented mitochondria and corresponding metabolic dysfunction. Targeting macrophage mitochondrial dynamics has proved to be an exciting potential therapeutic approach to combat vascular disease. This review will summarize mitochondrial and metabolic mechanisms of macrophage activation, polarization, and accumulation in vascular diseases.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"156 ","pages":"Article 107419"},"PeriodicalIF":3.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1537189124001459/pdfft?md5=6b29db26ffb2d1984f13c4a0b9fee3c4&pid=1-s2.0-S1537189124001459-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of a novel mitophagy-related 5-genes signature for diagnosis of acute myocardial infarction","authors":"Yanhua Xu ,&nbsp;Wenqing Zhu ,&nbsp;Yang Su ,&nbsp;Teng Ma ,&nbsp;Yaqi Zhang ,&nbsp;Xin Pan ,&nbsp;Rongrong Huang ,&nbsp;Yuhao Li ,&nbsp;Keqiang Zuo ,&nbsp;Sang-Bing Ong ,&nbsp;Dachun Xu","doi":"10.1016/j.vph.2024.107417","DOIUrl":"10.1016/j.vph.2024.107417","url":null,"abstract":"<div><p>Myocardial infarction (MI) and the ensuing heart failure (HF) remain the main cause of morbidity and mortality worldwide. One of the strategies to combat MI and HF lies in the ability to accurately predict the onset of these disorders. Alterations in mitochondrial homeostasis have been reported to be involved in the pathogenesis of various cardiovascular diseases (CVDs). In this regard, perturbations to mitochondrial dynamics leading to impaired clearance of dysfunctional mitochondria have been previously established to be a crucial trigger for MI/HF.</p><p>In this study, we found that MI patients could be classified into three clusters based on the expression levels of mitophagy-related genes and consensus clustering. We identified a mitophagy-related diagnostic 5-genes signature for MI using support vector machines-Recursive Feature Elimination (SVM-RFE) and random forest, with the area under the ROC curve (AUC) value of the predictive model at 0.813. Additionally, the single-cell transcriptome and pseudo-time analyses showed that the mitoscore was significantly upregulated in macrophages, endothelial cells, pericytes, fibroblasts and monocytes in patients with ischemic cardiomyopathy, while sequestosome 1 (SQSTM1) exhibited remarkable increase in the infarcted (ICM) and non-infarcted (ICMN) myocardium samples dissected from the left ventricle compared with control samples. Lastly, through analysis of peripheral blood from MI patients, we found that the expression of SQSTM1 is positively correlated with troponin-T (<em>P</em> &lt; 0.0001, <em>R</em> = 0.4195, R2 = 0.1759). Therefore, this study provides the rationale for a cell-specific mitophagy-related gene signature as an additional supporting diagnostic for CVDs.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"156 ","pages":"Article 107417"},"PeriodicalIF":3.5,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3-methoxycatechol causes vasodilation likely via KV channels: ex vivo, in silico docking and in vivo study","authors":"Patrícia Dias ,&nbsp;Rudy Salam ,&nbsp;Monika Moravcová ,&nbsp;Saina Saadat ,&nbsp;Jana Pourová ,&nbsp;Marie Vopršalová ,&nbsp;Eduard Jirkovský ,&nbsp;Jurjen Duintjer Tebbens ,&nbsp;Přemysl Mladěnka","doi":"10.1016/j.vph.2024.107418","DOIUrl":"10.1016/j.vph.2024.107418","url":null,"abstract":"<div><p>Substituted catechols include both natural and synthetic compounds found in the environment and foods. Some of them are flavonoid metabolites formed by the gut microbiota which are absorbed afterwards. Our previous findings showed that one of these metabolites, 4-methylcatechol, exerts potent vasorelaxant effects in rats. In the current study, we aimed at testing of its 22 structural congeners in order to find the most potent structure and to investigate the mechanism of action. 3-methoxycatechol (3-MOC), 4-ethylcatechol, 3,5-dichlorocatechol, 4-tert-butylcatechol, 4,5-dichlorocatechol, 3-fluorocatechol, 3-isopropylcatechol, 3-methylcatechol and the parent 4-methylcatechol exhibited high vasodilatory activities on isolated rat aortic rings with EC₅₀s ranging from ∼10 to 24 μM. Some significant sex-differences were found. The most potent compound, 3-MOC, relaxed also resistant mesenteric artery but not porcine coronary artery, and decreased arterial blood pressure in both male and female spontaneously hypertensive rats <em>in vivo</em> without affecting heart rate. It potentiated the vasodilation mediated by cAMP and cGMP, but did not impact L-type Ca²⁺-channels. By using two inhibitors, activation of voltage-gated potassium channels (K_V) was found to be involved in the mechanism of action. This was corroborated by docking analysis of 3-MOC with the K_V7.4 channel. None of the most active catechols decreased the viability of the A-10 rat embryonic thoracic aorta smooth muscle cell line. Our findings showed that various catechols can relax vascular smooth muscles and hence could provide templates for developing new antihypertensive vasodilator agents without affecting coronary circulation.</p></div>","PeriodicalId":23949,"journal":{"name":"Vascular pharmacology","volume":"156 ","pages":"Article 107418"},"PeriodicalIF":3.5,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}