Christian Staehr, Victoria Hinkley, Vladimir V. Matchkov, Rajkumar Rajanathan, Line Mathilde B. Hansen, Yvonne Eiby, Nathan Luque, Ian Wright, Stella T. Bjorkman, Stephanie M. Miller, Rohan S. Grimley, Andrew Dettrick, Kirat Chand, Hong L. Nguyen, Nicole M. Jones, Tim V. Murphy, Shaun L. Sandow
{"title":"缺氧和缺血性中风通过上调内皮细胞BK（Ca）通道来改变脑血管张力——来自大鼠、猪、小鼠和人的经验教训。","authors":"Christian Staehr, Victoria Hinkley, Vladimir V. Matchkov, Rajkumar Rajanathan, Line Mathilde B. Hansen, Yvonne Eiby, Nathan Luque, Ian Wright, Stella T. Bjorkman, Stephanie M. Miller, Rohan S. Grimley, Andrew Dettrick, Kirat Chand, Hong L. Nguyen, Nicole M. Jones, Tim V. Murphy, Shaun L. Sandow","doi":"10.1111/apha.70030","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aim</h3>\n \n <p>In animal models and human cerebral arteries, the changes in endothelial cell (EC)-large conductance calcium-activated potassium channel (BK<sub>Ca</sub>) distribution, expression, and function were determined in hypoxia and ischemic stroke. The hypothesis that hypoxia and ischemic stroke induce EC-BK<sub>Ca</sub> in cerebral arteries was examined.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Immunohistochemistry analyzed BK<sub>Ca</sub> expression in EC and smooth muscle (SM) of the middle-cerebral artery (MCA) from rat, piglet, and mouse, and pial arteriole of human. Pressure myography with pharmacological intervention characterized EC-BK<sub>Ca</sub> and TRPV4 function in rat MCA. Electron microscopy determined caveolae density and vessel properties in rat and mouse MCA.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>In rat, pig, and human cerebral vessels, EC-BK<sub>Ca</sub> was absent in normoxia; present after <i>chronic</i> (rat) and <i>acute</i> hypoxia (pig), post-ischemic stroke in human vessels, and after endothelin-1-induced stroke in rats. Mouse MCA EC-BK<sub>Ca</sub> expression increased after <i>acute</i> hypoxia. In rat MCA post-hypoxia and stroke, EC and SMC caveolae density increased, with reduced medial thickness, and unchanged diameter. Caveolae and BK<sub>Ca</sub> did not colocalize. In rat MCA, iberiotoxin (IbTx) potentiated pressure-induced tone in hypoxia/stroke, but not in normoxia. In normoxia, overall MCA tone was unaffected by endothelial removal, but was increased in hypoxia/stroke, where there was no additive effect of endothelial removal and IbTx on tone. Functional TRPV4 was expressed in EC of rat MCA post-stroke.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>In post-hypoxia/stroke, but not in normoxia, EC-BK<sub>Ca</sub> contribute to the regulation of MCA tone. Identifying unique up- and downstream signaling mechanisms associated with EC-BK<sub>Ca</sub> is a potential therapeutic target to control blood flow post-hypoxia/stroke.</p>\n </section>\n </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 4","pages":""},"PeriodicalIF":5.6000,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926774/pdf/","citationCount":"0","resultStr":"{\"title\":\"Hypoxia and ischemic stroke modify cerebrovascular tone by upregulating endothelial BK(Ca) channels—Lessons from rat, pig, mouse, and human\",\"authors\":\"Christian Staehr, Victoria Hinkley, Vladimir V. Matchkov, Rajkumar Rajanathan, Line Mathilde B. Hansen, Yvonne Eiby, Nathan Luque, Ian Wright, Stella T. Bjorkman, Stephanie M. Miller, Rohan S. Grimley, Andrew Dettrick, Kirat Chand, Hong L. Nguyen, Nicole M. Jones, Tim V. Murphy, Shaun L. Sandow\",\"doi\":\"10.1111/apha.70030\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Aim</h3>\\n \\n <p>In animal models and human cerebral arteries, the changes in endothelial cell (EC)-large conductance calcium-activated potassium channel (BK<sub>Ca</sub>) distribution, expression, and function were determined in hypoxia and ischemic stroke. The hypothesis that hypoxia and ischemic stroke induce EC-BK<sub>Ca</sub> in cerebral arteries was examined.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Immunohistochemistry analyzed BK<sub>Ca</sub> expression in EC and smooth muscle (SM) of the middle-cerebral artery (MCA) from rat, piglet, and mouse, and pial arteriole of human. Pressure myography with pharmacological intervention characterized EC-BK<sub>Ca</sub> and TRPV4 function in rat MCA. Electron microscopy determined caveolae density and vessel properties in rat and mouse MCA.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>In rat, pig, and human cerebral vessels, EC-BK<sub>Ca</sub> was absent in normoxia; present after <i>chronic</i> (rat) and <i>acute</i> hypoxia (pig), post-ischemic stroke in human vessels, and after endothelin-1-induced stroke in rats. Mouse MCA EC-BK<sub>Ca</sub> expression increased after <i>acute</i> hypoxia. In rat MCA post-hypoxia and stroke, EC and SMC caveolae density increased, with reduced medial thickness, and unchanged diameter. Caveolae and BK<sub>Ca</sub> did not colocalize. In rat MCA, iberiotoxin (IbTx) potentiated pressure-induced tone in hypoxia/stroke, but not in normoxia. In normoxia, overall MCA tone was unaffected by endothelial removal, but was increased in hypoxia/stroke, where there was no additive effect of endothelial removal and IbTx on tone. Functional TRPV4 was expressed in EC of rat MCA post-stroke.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>In post-hypoxia/stroke, but not in normoxia, EC-BK<sub>Ca</sub> contribute to the regulation of MCA tone. Identifying unique up- and downstream signaling mechanisms associated with EC-BK<sub>Ca</sub> is a potential therapeutic target to control blood flow post-hypoxia/stroke.</p>\\n </section>\\n </div>\",\"PeriodicalId\":107,\"journal\":{\"name\":\"Acta Physiologica\",\"volume\":\"241 4\",\"pages\":\"\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2025-03-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926774/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Physiologica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/apha.70030\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHYSIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Physiologica","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/apha.70030","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
Hypoxia and ischemic stroke modify cerebrovascular tone by upregulating endothelial BK(Ca) channels—Lessons from rat, pig, mouse, and human
Aim
In animal models and human cerebral arteries, the changes in endothelial cell (EC)-large conductance calcium-activated potassium channel (BKCa) distribution, expression, and function were determined in hypoxia and ischemic stroke. The hypothesis that hypoxia and ischemic stroke induce EC-BKCa in cerebral arteries was examined.
Methods
Immunohistochemistry analyzed BKCa expression in EC and smooth muscle (SM) of the middle-cerebral artery (MCA) from rat, piglet, and mouse, and pial arteriole of human. Pressure myography with pharmacological intervention characterized EC-BKCa and TRPV4 function in rat MCA. Electron microscopy determined caveolae density and vessel properties in rat and mouse MCA.
Results
In rat, pig, and human cerebral vessels, EC-BKCa was absent in normoxia; present after chronic (rat) and acute hypoxia (pig), post-ischemic stroke in human vessels, and after endothelin-1-induced stroke in rats. Mouse MCA EC-BKCa expression increased after acute hypoxia. In rat MCA post-hypoxia and stroke, EC and SMC caveolae density increased, with reduced medial thickness, and unchanged diameter. Caveolae and BKCa did not colocalize. In rat MCA, iberiotoxin (IbTx) potentiated pressure-induced tone in hypoxia/stroke, but not in normoxia. In normoxia, overall MCA tone was unaffected by endothelial removal, but was increased in hypoxia/stroke, where there was no additive effect of endothelial removal and IbTx on tone. Functional TRPV4 was expressed in EC of rat MCA post-stroke.
Conclusions
In post-hypoxia/stroke, but not in normoxia, EC-BKCa contribute to the regulation of MCA tone. Identifying unique up- and downstream signaling mechanisms associated with EC-BKCa is a potential therapeutic target to control blood flow post-hypoxia/stroke.
期刊介绍：
Acta Physiologica is an important forum for the publication of high quality original research in physiology and related areas by authors from all over the world. Acta Physiologica is a leading journal in human/translational physiology while promoting all aspects of the science of physiology. The journal publishes full length original articles on important new observations as well as reviews and commentaries.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
