Hypoxia and ischemic stroke modify cerebrovascular tone by upregulating endothelial BK(Ca) channels—Lessons from rat, pig, mouse, and human.
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| Title: | Hypoxia and ischemic stroke modify cerebrovascular tone by upregulating endothelial BK(Ca) channels—Lessons from rat, pig, mouse, and human. |
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| Authors: | Staehr, Christian (AUTHOR), Hinkley, Victoria (AUTHOR), Matchkov, Vladimir V. (AUTHOR), Rajanathan, Rajkumar (AUTHOR), Hansen, Line Mathilde B. (AUTHOR), Eiby, Yvonne (AUTHOR), Luque, Nathan (AUTHOR), Wright, Ian (AUTHOR), Bjorkman, Stella T. (AUTHOR), Miller, Stephanie M. (AUTHOR), Grimley, Rohan S. (AUTHOR), Dettrick, Andrew (AUTHOR), Chand, Kirat (AUTHOR), Nguyen, Hong L. (AUTHOR), Jones, Nicole M. (AUTHOR), Murphy, Tim V. (AUTHOR), Sandow, Shaun L. (AUTHOR) |
| Source: | Acta Physiologica. Apr2025, Vol. 241 Issue 4, p1-12. 12p. |
| Subjects: | Ischemic stroke, Cerebral arteries, Drug target, Animal models in research, Hypoxemia, Vascular smooth muscle, Ion channels |
| Abstract: | 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. [ABSTRACT FROM AUTHOR] |
| Copyright of Acta Physiologica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 184106839 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Hypoxia and ischemic stroke modify cerebrovascular tone by upregulating endothelial BK(Ca) channels—Lessons from rat, pig, mouse, and human. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Staehr%2C+Christian%22">Staehr, Christian</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hinkley%2C+Victoria%22">Hinkley, Victoria</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Matchkov%2C+Vladimir+V%2E%22">Matchkov, Vladimir V.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rajanathan%2C+Rajkumar%22">Rajanathan, Rajkumar</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hansen%2C+Line+Mathilde+B%2E%22">Hansen, Line Mathilde B.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Eiby%2C+Yvonne%22">Eiby, Yvonne</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Luque%2C+Nathan%22">Luque, Nathan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wright%2C+Ian%22">Wright, Ian</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bjorkman%2C+Stella+T%2E%22">Bjorkman, Stella T.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Miller%2C+Stephanie+M%2E%22">Miller, Stephanie M.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Grimley%2C+Rohan+S%2E%22">Grimley, Rohan S.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dettrick%2C+Andrew%22">Dettrick, Andrew</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chand%2C+Kirat%22">Chand, Kirat</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Nguyen%2C+Hong+L%2E%22">Nguyen, Hong L.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Jones%2C+Nicole+M%2E%22">Jones, Nicole M.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Murphy%2C+Tim+V%2E%22">Murphy, Tim V.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sandow%2C+Shaun+L%2E%22">Sandow, Shaun L.</searchLink> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Acta+Physiologica%22">Acta Physiologica</searchLink>. Apr2025, Vol. 241 Issue 4, p1-12. 12p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Ischemic+stroke%22">Ischemic stroke</searchLink><br /><searchLink fieldCode="DE" term="%22Cerebral+arteries%22">Cerebral arteries</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+target%22">Drug target</searchLink><br /><searchLink fieldCode="DE" term="%22Animal+models+in+research%22">Animal models in research</searchLink><br /><searchLink fieldCode="DE" term="%22Hypoxemia%22">Hypoxemia</searchLink><br /><searchLink fieldCode="DE" term="%22Vascular+smooth+muscle%22">Vascular smooth muscle</searchLink><br /><searchLink fieldCode="DE" term="%22Ion+channels%22">Ion channels</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: 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. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Acta Physiologica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1111/apha.70030 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 12 StartPage: 1 Subjects: – SubjectFull: Ischemic stroke Type: general – SubjectFull: Cerebral arteries Type: general – SubjectFull: Drug target Type: general – SubjectFull: Animal models in research Type: general – SubjectFull: Hypoxemia Type: general – SubjectFull: Vascular smooth muscle Type: general – SubjectFull: Ion channels Type: general Titles: – TitleFull: Hypoxia and ischemic stroke modify cerebrovascular tone by upregulating endothelial BK(Ca) channels—Lessons from rat, pig, mouse, and human. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Staehr, Christian – PersonEntity: Name: NameFull: Hinkley, Victoria – PersonEntity: Name: NameFull: Matchkov, Vladimir V. – PersonEntity: Name: NameFull: Rajanathan, Rajkumar – PersonEntity: Name: NameFull: Hansen, Line Mathilde B. – PersonEntity: Name: NameFull: Eiby, Yvonne – PersonEntity: Name: NameFull: Luque, Nathan – PersonEntity: Name: NameFull: Wright, Ian – PersonEntity: Name: NameFull: Bjorkman, Stella T. – PersonEntity: Name: NameFull: Miller, Stephanie M. – PersonEntity: Name: NameFull: Grimley, Rohan S. – PersonEntity: Name: NameFull: Dettrick, Andrew – PersonEntity: Name: NameFull: Chand, Kirat – PersonEntity: Name: NameFull: Nguyen, Hong L. – PersonEntity: Name: NameFull: Jones, Nicole M. – PersonEntity: Name: NameFull: Murphy, Tim V. – PersonEntity: Name: NameFull: Sandow, Shaun L. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 04 Text: Apr2025 Type: published Y: 2025 Identifiers: – Type: issn-print Value: 17481708 Numbering: – Type: volume Value: 241 – Type: issue Value: 4 Titles: – TitleFull: Acta Physiologica Type: main |
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