Endothelin B receptor dysfunction mediates elevated myogenic tone in cerebral arteries from aged male Fischer 344 rats
Abstract The human brain requires adequate cerebral blood flow to meet the high demand for nutrients and to clear waste products. With age, there is a chronic reduction in cerebral blood flow in small resistance arteries that can eventually limit proper brain function. The endothelin system is a key...
Ausführliche Beschreibung
Autor*in: |
Young, Alexander P. [verfasserIn] Zhu, Jiequan [verfasserIn] Bagher, Amina M. [verfasserIn] Denovan-Wright, Eileen M. [verfasserIn] Howlett, Susan E. [verfasserIn] Kelly, Melanie E.M. [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2021 |
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Schlagwörter: |
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Anmerkung: |
© American Aging Association 2021 |
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Übergeordnetes Werk: |
Enthalten in: Age - New York, NY : Springer Science+Business Media, 1978, 43(2021), 3 vom: 05. Jan., Seite 1447-1463 |
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Übergeordnetes Werk: |
volume:43 ; year:2021 ; number:3 ; day:05 ; month:01 ; pages:1447-1463 |
Links: |
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DOI / URN: |
10.1007/s11357-020-00309-7 |
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Katalog-ID: |
SPR044262167 |
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520 | |a Abstract The human brain requires adequate cerebral blood flow to meet the high demand for nutrients and to clear waste products. With age, there is a chronic reduction in cerebral blood flow in small resistance arteries that can eventually limit proper brain function. The endothelin system is a key mediator in the regulation of cerebral blood flow, but the contributions of its constituent receptors in the endothelial and vascular smooth muscle layers of cerebral arteries have not been well defined in the context of aging. We isolated posterior cerebral arteries from young and aged Fischer 344 rats, as well as $ ET_{B} $ receptor knock-out rats and mounted the vessels in plexiglass pressure myograph chambers to measure myogenic tone in response to increasing pressure and targeted pharmacological treatments. We used an $ ET_{A} $ receptor antagonist (BQ-123), an $ ET_{B} $ receptor antagonist (BQ-788), endothelin-1, an endothelin-1 synthesis inhibitor (phosphoramidon), and vessel denudation to dissect the roles of each receptor in aging vasculature. Aged rats exhibited a higher myogenic tone than young rats, and the tone was sensitive to the $ ET_{A} $ antagonist, BQ-123, but insensitive to the $ ET_{B} $ antagonist, BQ-788. By contrast, the tone in the vessels from young rats was raised by BQ-788 but unaffected by BQ-123. When the endothelial layer that is normally enriched with $ ET_{B1} $ receptors was removed from young vessels, myogenic tone increased. However, denudation of the endothelial layer did not influence vessels from aged animals. This indicated that endothelial $ ET_{B1} $ receptors were not functional in the vessels from aged rats. There was also an increase in $ ET_{A} $ receptor expression with age, whereas $ ET_{B} $ receptor expression remained constant between young and aged animals. These results demonstrate that in young vessels, $ ET_{B1} $ receptors maintain a lower myogenic tone, but in aged vessels, a loss of $ ET_{B} $ receptor activity allows $ ET_{A} $ receptors in vascular smooth muscle cells to raise myogenic tone. Our findings have potentially important clinical implications for treatments to improve cerebral perfusion in older adults with diseases characterized by reduced cerebral blood flow. | ||
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10.1007/s11357-020-00309-7 doi (DE-627)SPR044262167 (SPR)s11357-020-00309-7-e DE-627 ger DE-627 rakwb eng 610 ASE 44.68 bkl Young, Alexander P. verfasserin aut Endothelin B receptor dysfunction mediates elevated myogenic tone in cerebral arteries from aged male Fischer 344 rats 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © American Aging Association 2021 Abstract The human brain requires adequate cerebral blood flow to meet the high demand for nutrients and to clear waste products. With age, there is a chronic reduction in cerebral blood flow in small resistance arteries that can eventually limit proper brain function. The endothelin system is a key mediator in the regulation of cerebral blood flow, but the contributions of its constituent receptors in the endothelial and vascular smooth muscle layers of cerebral arteries have not been well defined in the context of aging. We isolated posterior cerebral arteries from young and aged Fischer 344 rats, as well as $ ET_{B} $ receptor knock-out rats and mounted the vessels in plexiglass pressure myograph chambers to measure myogenic tone in response to increasing pressure and targeted pharmacological treatments. We used an $ ET_{A} $ receptor antagonist (BQ-123), an $ ET_{B} $ receptor antagonist (BQ-788), endothelin-1, an endothelin-1 synthesis inhibitor (phosphoramidon), and vessel denudation to dissect the roles of each receptor in aging vasculature. Aged rats exhibited a higher myogenic tone than young rats, and the tone was sensitive to the $ ET_{A} $ antagonist, BQ-123, but insensitive to the $ ET_{B} $ antagonist, BQ-788. By contrast, the tone in the vessels from young rats was raised by BQ-788 but unaffected by BQ-123. When the endothelial layer that is normally enriched with $ ET_{B1} $ receptors was removed from young vessels, myogenic tone increased. However, denudation of the endothelial layer did not influence vessels from aged animals. This indicated that endothelial $ ET_{B1} $ receptors were not functional in the vessels from aged rats. There was also an increase in $ ET_{A} $ receptor expression with age, whereas $ ET_{B} $ receptor expression remained constant between young and aged animals. These results demonstrate that in young vessels, $ ET_{B1} $ receptors maintain a lower myogenic tone, but in aged vessels, a loss of $ ET_{B} $ receptor activity allows $ ET_{A} $ receptors in vascular smooth muscle cells to raise myogenic tone. Our findings have potentially important clinical implications for treatments to improve cerebral perfusion in older adults with diseases characterized by reduced cerebral blood flow. ET (dpeaa)DE-He213 receptors (dpeaa)DE-He213 ET (dpeaa)DE-He213 receptors (dpeaa)DE-He213 Fischer 344 rats (dpeaa)DE-He213 Myogenic tone (dpeaa)DE-He213 Cerebral artery (dpeaa)DE-He213 Zhu, Jiequan verfasserin aut Bagher, Amina M. verfasserin aut Denovan-Wright, Eileen M. verfasserin aut Howlett, Susan E. verfasserin aut Kelly, Melanie E.M. verfasserin aut Enthalten in Age New York, NY : Springer Science+Business Media, 1978 43(2021), 3 vom: 05. Jan., Seite 1447-1463 (DE-627)499546180 (DE-600)2201958-3 1574-4647 nnns volume:43 year:2021 number:3 day:05 month:01 pages:1447-1463 https://dx.doi.org/10.1007/s11357-020-00309-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_40 GBV_ILN_60 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_110 GBV_ILN_120 GBV_ILN_161 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 44.68 ASE AR 43 2021 3 05 01 1447-1463 |
spelling |
10.1007/s11357-020-00309-7 doi (DE-627)SPR044262167 (SPR)s11357-020-00309-7-e DE-627 ger DE-627 rakwb eng 610 ASE 44.68 bkl Young, Alexander P. verfasserin aut Endothelin B receptor dysfunction mediates elevated myogenic tone in cerebral arteries from aged male Fischer 344 rats 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © American Aging Association 2021 Abstract The human brain requires adequate cerebral blood flow to meet the high demand for nutrients and to clear waste products. With age, there is a chronic reduction in cerebral blood flow in small resistance arteries that can eventually limit proper brain function. The endothelin system is a key mediator in the regulation of cerebral blood flow, but the contributions of its constituent receptors in the endothelial and vascular smooth muscle layers of cerebral arteries have not been well defined in the context of aging. We isolated posterior cerebral arteries from young and aged Fischer 344 rats, as well as $ ET_{B} $ receptor knock-out rats and mounted the vessels in plexiglass pressure myograph chambers to measure myogenic tone in response to increasing pressure and targeted pharmacological treatments. We used an $ ET_{A} $ receptor antagonist (BQ-123), an $ ET_{B} $ receptor antagonist (BQ-788), endothelin-1, an endothelin-1 synthesis inhibitor (phosphoramidon), and vessel denudation to dissect the roles of each receptor in aging vasculature. Aged rats exhibited a higher myogenic tone than young rats, and the tone was sensitive to the $ ET_{A} $ antagonist, BQ-123, but insensitive to the $ ET_{B} $ antagonist, BQ-788. By contrast, the tone in the vessels from young rats was raised by BQ-788 but unaffected by BQ-123. When the endothelial layer that is normally enriched with $ ET_{B1} $ receptors was removed from young vessels, myogenic tone increased. However, denudation of the endothelial layer did not influence vessels from aged animals. This indicated that endothelial $ ET_{B1} $ receptors were not functional in the vessels from aged rats. There was also an increase in $ ET_{A} $ receptor expression with age, whereas $ ET_{B} $ receptor expression remained constant between young and aged animals. These results demonstrate that in young vessels, $ ET_{B1} $ receptors maintain a lower myogenic tone, but in aged vessels, a loss of $ ET_{B} $ receptor activity allows $ ET_{A} $ receptors in vascular smooth muscle cells to raise myogenic tone. Our findings have potentially important clinical implications for treatments to improve cerebral perfusion in older adults with diseases characterized by reduced cerebral blood flow. ET (dpeaa)DE-He213 receptors (dpeaa)DE-He213 ET (dpeaa)DE-He213 receptors (dpeaa)DE-He213 Fischer 344 rats (dpeaa)DE-He213 Myogenic tone (dpeaa)DE-He213 Cerebral artery (dpeaa)DE-He213 Zhu, Jiequan verfasserin aut Bagher, Amina M. verfasserin aut Denovan-Wright, Eileen M. verfasserin aut Howlett, Susan E. verfasserin aut Kelly, Melanie E.M. verfasserin aut Enthalten in Age New York, NY : Springer Science+Business Media, 1978 43(2021), 3 vom: 05. Jan., Seite 1447-1463 (DE-627)499546180 (DE-600)2201958-3 1574-4647 nnns volume:43 year:2021 number:3 day:05 month:01 pages:1447-1463 https://dx.doi.org/10.1007/s11357-020-00309-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_40 GBV_ILN_60 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_110 GBV_ILN_120 GBV_ILN_161 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 44.68 ASE AR 43 2021 3 05 01 1447-1463 |
allfields_unstemmed |
10.1007/s11357-020-00309-7 doi (DE-627)SPR044262167 (SPR)s11357-020-00309-7-e DE-627 ger DE-627 rakwb eng 610 ASE 44.68 bkl Young, Alexander P. verfasserin aut Endothelin B receptor dysfunction mediates elevated myogenic tone in cerebral arteries from aged male Fischer 344 rats 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © American Aging Association 2021 Abstract The human brain requires adequate cerebral blood flow to meet the high demand for nutrients and to clear waste products. With age, there is a chronic reduction in cerebral blood flow in small resistance arteries that can eventually limit proper brain function. The endothelin system is a key mediator in the regulation of cerebral blood flow, but the contributions of its constituent receptors in the endothelial and vascular smooth muscle layers of cerebral arteries have not been well defined in the context of aging. We isolated posterior cerebral arteries from young and aged Fischer 344 rats, as well as $ ET_{B} $ receptor knock-out rats and mounted the vessels in plexiglass pressure myograph chambers to measure myogenic tone in response to increasing pressure and targeted pharmacological treatments. We used an $ ET_{A} $ receptor antagonist (BQ-123), an $ ET_{B} $ receptor antagonist (BQ-788), endothelin-1, an endothelin-1 synthesis inhibitor (phosphoramidon), and vessel denudation to dissect the roles of each receptor in aging vasculature. Aged rats exhibited a higher myogenic tone than young rats, and the tone was sensitive to the $ ET_{A} $ antagonist, BQ-123, but insensitive to the $ ET_{B} $ antagonist, BQ-788. By contrast, the tone in the vessels from young rats was raised by BQ-788 but unaffected by BQ-123. When the endothelial layer that is normally enriched with $ ET_{B1} $ receptors was removed from young vessels, myogenic tone increased. However, denudation of the endothelial layer did not influence vessels from aged animals. This indicated that endothelial $ ET_{B1} $ receptors were not functional in the vessels from aged rats. There was also an increase in $ ET_{A} $ receptor expression with age, whereas $ ET_{B} $ receptor expression remained constant between young and aged animals. These results demonstrate that in young vessels, $ ET_{B1} $ receptors maintain a lower myogenic tone, but in aged vessels, a loss of $ ET_{B} $ receptor activity allows $ ET_{A} $ receptors in vascular smooth muscle cells to raise myogenic tone. Our findings have potentially important clinical implications for treatments to improve cerebral perfusion in older adults with diseases characterized by reduced cerebral blood flow. ET (dpeaa)DE-He213 receptors (dpeaa)DE-He213 ET (dpeaa)DE-He213 receptors (dpeaa)DE-He213 Fischer 344 rats (dpeaa)DE-He213 Myogenic tone (dpeaa)DE-He213 Cerebral artery (dpeaa)DE-He213 Zhu, Jiequan verfasserin aut Bagher, Amina M. verfasserin aut Denovan-Wright, Eileen M. verfasserin aut Howlett, Susan E. verfasserin aut Kelly, Melanie E.M. verfasserin aut Enthalten in Age New York, NY : Springer Science+Business Media, 1978 43(2021), 3 vom: 05. Jan., Seite 1447-1463 (DE-627)499546180 (DE-600)2201958-3 1574-4647 nnns volume:43 year:2021 number:3 day:05 month:01 pages:1447-1463 https://dx.doi.org/10.1007/s11357-020-00309-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_40 GBV_ILN_60 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_110 GBV_ILN_120 GBV_ILN_161 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 44.68 ASE AR 43 2021 3 05 01 1447-1463 |
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10.1007/s11357-020-00309-7 doi (DE-627)SPR044262167 (SPR)s11357-020-00309-7-e DE-627 ger DE-627 rakwb eng 610 ASE 44.68 bkl Young, Alexander P. verfasserin aut Endothelin B receptor dysfunction mediates elevated myogenic tone in cerebral arteries from aged male Fischer 344 rats 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © American Aging Association 2021 Abstract The human brain requires adequate cerebral blood flow to meet the high demand for nutrients and to clear waste products. With age, there is a chronic reduction in cerebral blood flow in small resistance arteries that can eventually limit proper brain function. The endothelin system is a key mediator in the regulation of cerebral blood flow, but the contributions of its constituent receptors in the endothelial and vascular smooth muscle layers of cerebral arteries have not been well defined in the context of aging. We isolated posterior cerebral arteries from young and aged Fischer 344 rats, as well as $ ET_{B} $ receptor knock-out rats and mounted the vessels in plexiglass pressure myograph chambers to measure myogenic tone in response to increasing pressure and targeted pharmacological treatments. We used an $ ET_{A} $ receptor antagonist (BQ-123), an $ ET_{B} $ receptor antagonist (BQ-788), endothelin-1, an endothelin-1 synthesis inhibitor (phosphoramidon), and vessel denudation to dissect the roles of each receptor in aging vasculature. Aged rats exhibited a higher myogenic tone than young rats, and the tone was sensitive to the $ ET_{A} $ antagonist, BQ-123, but insensitive to the $ ET_{B} $ antagonist, BQ-788. By contrast, the tone in the vessels from young rats was raised by BQ-788 but unaffected by BQ-123. When the endothelial layer that is normally enriched with $ ET_{B1} $ receptors was removed from young vessels, myogenic tone increased. However, denudation of the endothelial layer did not influence vessels from aged animals. This indicated that endothelial $ ET_{B1} $ receptors were not functional in the vessels from aged rats. There was also an increase in $ ET_{A} $ receptor expression with age, whereas $ ET_{B} $ receptor expression remained constant between young and aged animals. These results demonstrate that in young vessels, $ ET_{B1} $ receptors maintain a lower myogenic tone, but in aged vessels, a loss of $ ET_{B} $ receptor activity allows $ ET_{A} $ receptors in vascular smooth muscle cells to raise myogenic tone. Our findings have potentially important clinical implications for treatments to improve cerebral perfusion in older adults with diseases characterized by reduced cerebral blood flow. ET (dpeaa)DE-He213 receptors (dpeaa)DE-He213 ET (dpeaa)DE-He213 receptors (dpeaa)DE-He213 Fischer 344 rats (dpeaa)DE-He213 Myogenic tone (dpeaa)DE-He213 Cerebral artery (dpeaa)DE-He213 Zhu, Jiequan verfasserin aut Bagher, Amina M. verfasserin aut Denovan-Wright, Eileen M. verfasserin aut Howlett, Susan E. verfasserin aut Kelly, Melanie E.M. verfasserin aut Enthalten in Age New York, NY : Springer Science+Business Media, 1978 43(2021), 3 vom: 05. Jan., Seite 1447-1463 (DE-627)499546180 (DE-600)2201958-3 1574-4647 nnns volume:43 year:2021 number:3 day:05 month:01 pages:1447-1463 https://dx.doi.org/10.1007/s11357-020-00309-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_40 GBV_ILN_60 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_110 GBV_ILN_120 GBV_ILN_161 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 44.68 ASE AR 43 2021 3 05 01 1447-1463 |
allfieldsSound |
10.1007/s11357-020-00309-7 doi (DE-627)SPR044262167 (SPR)s11357-020-00309-7-e DE-627 ger DE-627 rakwb eng 610 ASE 44.68 bkl Young, Alexander P. verfasserin aut Endothelin B receptor dysfunction mediates elevated myogenic tone in cerebral arteries from aged male Fischer 344 rats 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © American Aging Association 2021 Abstract The human brain requires adequate cerebral blood flow to meet the high demand for nutrients and to clear waste products. With age, there is a chronic reduction in cerebral blood flow in small resistance arteries that can eventually limit proper brain function. The endothelin system is a key mediator in the regulation of cerebral blood flow, but the contributions of its constituent receptors in the endothelial and vascular smooth muscle layers of cerebral arteries have not been well defined in the context of aging. We isolated posterior cerebral arteries from young and aged Fischer 344 rats, as well as $ ET_{B} $ receptor knock-out rats and mounted the vessels in plexiglass pressure myograph chambers to measure myogenic tone in response to increasing pressure and targeted pharmacological treatments. We used an $ ET_{A} $ receptor antagonist (BQ-123), an $ ET_{B} $ receptor antagonist (BQ-788), endothelin-1, an endothelin-1 synthesis inhibitor (phosphoramidon), and vessel denudation to dissect the roles of each receptor in aging vasculature. Aged rats exhibited a higher myogenic tone than young rats, and the tone was sensitive to the $ ET_{A} $ antagonist, BQ-123, but insensitive to the $ ET_{B} $ antagonist, BQ-788. By contrast, the tone in the vessels from young rats was raised by BQ-788 but unaffected by BQ-123. When the endothelial layer that is normally enriched with $ ET_{B1} $ receptors was removed from young vessels, myogenic tone increased. However, denudation of the endothelial layer did not influence vessels from aged animals. This indicated that endothelial $ ET_{B1} $ receptors were not functional in the vessels from aged rats. There was also an increase in $ ET_{A} $ receptor expression with age, whereas $ ET_{B} $ receptor expression remained constant between young and aged animals. These results demonstrate that in young vessels, $ ET_{B1} $ receptors maintain a lower myogenic tone, but in aged vessels, a loss of $ ET_{B} $ receptor activity allows $ ET_{A} $ receptors in vascular smooth muscle cells to raise myogenic tone. Our findings have potentially important clinical implications for treatments to improve cerebral perfusion in older adults with diseases characterized by reduced cerebral blood flow. ET (dpeaa)DE-He213 receptors (dpeaa)DE-He213 ET (dpeaa)DE-He213 receptors (dpeaa)DE-He213 Fischer 344 rats (dpeaa)DE-He213 Myogenic tone (dpeaa)DE-He213 Cerebral artery (dpeaa)DE-He213 Zhu, Jiequan verfasserin aut Bagher, Amina M. verfasserin aut Denovan-Wright, Eileen M. verfasserin aut Howlett, Susan E. verfasserin aut Kelly, Melanie E.M. verfasserin aut Enthalten in Age New York, NY : Springer Science+Business Media, 1978 43(2021), 3 vom: 05. Jan., Seite 1447-1463 (DE-627)499546180 (DE-600)2201958-3 1574-4647 nnns volume:43 year:2021 number:3 day:05 month:01 pages:1447-1463 https://dx.doi.org/10.1007/s11357-020-00309-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_40 GBV_ILN_60 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_110 GBV_ILN_120 GBV_ILN_161 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 44.68 ASE AR 43 2021 3 05 01 1447-1463 |
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Young, Alexander P. @@aut@@ Zhu, Jiequan @@aut@@ Bagher, Amina M. @@aut@@ Denovan-Wright, Eileen M. @@aut@@ Howlett, Susan E. @@aut@@ Kelly, Melanie E.M. @@aut@@ |
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Young, Alexander P. ddc 610 bkl 44.68 misc ET misc receptors misc Fischer 344 rats misc Myogenic tone misc Cerebral artery Endothelin B receptor dysfunction mediates elevated myogenic tone in cerebral arteries from aged male Fischer 344 rats |
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610 ASE 44.68 bkl Endothelin B receptor dysfunction mediates elevated myogenic tone in cerebral arteries from aged male Fischer 344 rats ET (dpeaa)DE-He213 receptors (dpeaa)DE-He213 Fischer 344 rats (dpeaa)DE-He213 Myogenic tone (dpeaa)DE-He213 Cerebral artery (dpeaa)DE-He213 |
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endothelin b receptor dysfunction mediates elevated myogenic tone in cerebral arteries from aged male fischer 344 rats |
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Endothelin B receptor dysfunction mediates elevated myogenic tone in cerebral arteries from aged male Fischer 344 rats |
abstract |
Abstract The human brain requires adequate cerebral blood flow to meet the high demand for nutrients and to clear waste products. With age, there is a chronic reduction in cerebral blood flow in small resistance arteries that can eventually limit proper brain function. The endothelin system is a key mediator in the regulation of cerebral blood flow, but the contributions of its constituent receptors in the endothelial and vascular smooth muscle layers of cerebral arteries have not been well defined in the context of aging. We isolated posterior cerebral arteries from young and aged Fischer 344 rats, as well as $ ET_{B} $ receptor knock-out rats and mounted the vessels in plexiglass pressure myograph chambers to measure myogenic tone in response to increasing pressure and targeted pharmacological treatments. We used an $ ET_{A} $ receptor antagonist (BQ-123), an $ ET_{B} $ receptor antagonist (BQ-788), endothelin-1, an endothelin-1 synthesis inhibitor (phosphoramidon), and vessel denudation to dissect the roles of each receptor in aging vasculature. Aged rats exhibited a higher myogenic tone than young rats, and the tone was sensitive to the $ ET_{A} $ antagonist, BQ-123, but insensitive to the $ ET_{B} $ antagonist, BQ-788. By contrast, the tone in the vessels from young rats was raised by BQ-788 but unaffected by BQ-123. When the endothelial layer that is normally enriched with $ ET_{B1} $ receptors was removed from young vessels, myogenic tone increased. However, denudation of the endothelial layer did not influence vessels from aged animals. This indicated that endothelial $ ET_{B1} $ receptors were not functional in the vessels from aged rats. There was also an increase in $ ET_{A} $ receptor expression with age, whereas $ ET_{B} $ receptor expression remained constant between young and aged animals. These results demonstrate that in young vessels, $ ET_{B1} $ receptors maintain a lower myogenic tone, but in aged vessels, a loss of $ ET_{B} $ receptor activity allows $ ET_{A} $ receptors in vascular smooth muscle cells to raise myogenic tone. Our findings have potentially important clinical implications for treatments to improve cerebral perfusion in older adults with diseases characterized by reduced cerebral blood flow. © American Aging Association 2021 |
abstractGer |
Abstract The human brain requires adequate cerebral blood flow to meet the high demand for nutrients and to clear waste products. With age, there is a chronic reduction in cerebral blood flow in small resistance arteries that can eventually limit proper brain function. The endothelin system is a key mediator in the regulation of cerebral blood flow, but the contributions of its constituent receptors in the endothelial and vascular smooth muscle layers of cerebral arteries have not been well defined in the context of aging. We isolated posterior cerebral arteries from young and aged Fischer 344 rats, as well as $ ET_{B} $ receptor knock-out rats and mounted the vessels in plexiglass pressure myograph chambers to measure myogenic tone in response to increasing pressure and targeted pharmacological treatments. We used an $ ET_{A} $ receptor antagonist (BQ-123), an $ ET_{B} $ receptor antagonist (BQ-788), endothelin-1, an endothelin-1 synthesis inhibitor (phosphoramidon), and vessel denudation to dissect the roles of each receptor in aging vasculature. Aged rats exhibited a higher myogenic tone than young rats, and the tone was sensitive to the $ ET_{A} $ antagonist, BQ-123, but insensitive to the $ ET_{B} $ antagonist, BQ-788. By contrast, the tone in the vessels from young rats was raised by BQ-788 but unaffected by BQ-123. When the endothelial layer that is normally enriched with $ ET_{B1} $ receptors was removed from young vessels, myogenic tone increased. However, denudation of the endothelial layer did not influence vessels from aged animals. This indicated that endothelial $ ET_{B1} $ receptors were not functional in the vessels from aged rats. There was also an increase in $ ET_{A} $ receptor expression with age, whereas $ ET_{B} $ receptor expression remained constant between young and aged animals. These results demonstrate that in young vessels, $ ET_{B1} $ receptors maintain a lower myogenic tone, but in aged vessels, a loss of $ ET_{B} $ receptor activity allows $ ET_{A} $ receptors in vascular smooth muscle cells to raise myogenic tone. Our findings have potentially important clinical implications for treatments to improve cerebral perfusion in older adults with diseases characterized by reduced cerebral blood flow. © American Aging Association 2021 |
abstract_unstemmed |
Abstract The human brain requires adequate cerebral blood flow to meet the high demand for nutrients and to clear waste products. With age, there is a chronic reduction in cerebral blood flow in small resistance arteries that can eventually limit proper brain function. The endothelin system is a key mediator in the regulation of cerebral blood flow, but the contributions of its constituent receptors in the endothelial and vascular smooth muscle layers of cerebral arteries have not been well defined in the context of aging. We isolated posterior cerebral arteries from young and aged Fischer 344 rats, as well as $ ET_{B} $ receptor knock-out rats and mounted the vessels in plexiglass pressure myograph chambers to measure myogenic tone in response to increasing pressure and targeted pharmacological treatments. We used an $ ET_{A} $ receptor antagonist (BQ-123), an $ ET_{B} $ receptor antagonist (BQ-788), endothelin-1, an endothelin-1 synthesis inhibitor (phosphoramidon), and vessel denudation to dissect the roles of each receptor in aging vasculature. Aged rats exhibited a higher myogenic tone than young rats, and the tone was sensitive to the $ ET_{A} $ antagonist, BQ-123, but insensitive to the $ ET_{B} $ antagonist, BQ-788. By contrast, the tone in the vessels from young rats was raised by BQ-788 but unaffected by BQ-123. When the endothelial layer that is normally enriched with $ ET_{B1} $ receptors was removed from young vessels, myogenic tone increased. However, denudation of the endothelial layer did not influence vessels from aged animals. This indicated that endothelial $ ET_{B1} $ receptors were not functional in the vessels from aged rats. There was also an increase in $ ET_{A} $ receptor expression with age, whereas $ ET_{B} $ receptor expression remained constant between young and aged animals. These results demonstrate that in young vessels, $ ET_{B1} $ receptors maintain a lower myogenic tone, but in aged vessels, a loss of $ ET_{B} $ receptor activity allows $ ET_{A} $ receptors in vascular smooth muscle cells to raise myogenic tone. Our findings have potentially important clinical implications for treatments to improve cerebral perfusion in older adults with diseases characterized by reduced cerebral blood flow. © American Aging Association 2021 |
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