Role of chymase in blood pressure control, plasma and tissue angiotensin II, renal Haemodynamics, and excretion in spontaneously hypertensive rats
Background: Chymase generates angiotensin II (ANG II) independently of angiotensin-converting enzyme in tissues and it contributes to vascular remodeling and development of hypertension, however the exact mechanism of its action is unclear. Methods: Hence, the effects of chymase inhibition were exam...
Ausführliche Beschreibung
Autor*in: |
Malwina M. Roszkowska-Chojecka [verfasserIn] Iwona Baranowska [verfasserIn] Olga Gawrys [verfasserIn] Janusz Sadowski [verfasserIn] Agnieszka Walkowska [verfasserIn] Malgorzata Kalisz [verfasserIn] Anna Litwiniuk [verfasserIn] Elzbieta Kompanowska-Jezierska [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2021 |
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Übergeordnetes Werk: |
In: Clinical and Experimental Hypertension - Taylor & Francis Group, 2023, 43(2021), 5, Seite 392-401 |
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Übergeordnetes Werk: |
volume:43 ; year:2021 ; number:5 ; pages:392-401 |
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Link aufrufen |
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DOI / URN: |
10.1080/10641963.2021.1890762 |
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Katalog-ID: |
DOAJ099473720 |
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520 | |a Background: Chymase generates angiotensin II (ANG II) independently of angiotensin-converting enzyme in tissues and it contributes to vascular remodeling and development of hypertension, however the exact mechanism of its action is unclear. Methods: Hence, the effects of chymase inhibition were examined in anesthetized spontaneously hypertensive rats (SHR) in two stages of the disease development, ie. pre-hypertensive (SHR7) and with established hypertension (SHR16). Chymostatin, a commercial chymase inhibitor, was infused intravenously alone or in subsequent groups co-infused with captopril. Results: Mean blood pressure (MBP), total renal blood flow (RBF) and ANG II content (plasma and tissues) were measured. In SHR16 chymase blockade significantly decreased MBP (−6%) and plasma (−38%), kidney (−71%) and heart (−52%) ANG II levels. In SHR7 chymostatin did not influence MBP or RBF, but significantly decreased heart ANG II level. Conclusion: Jointly, functional studies and ANG II determinations support the evidence that in SHR chymase can raise plasma ANG II and contribute to blood pressure elevation. We propose that addition of chymase blockade to ACE inhibition could be a promising approach in the treatment of hypertensive patients resistant to therapy with ACE-inhibitors alone. | ||
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10.1080/10641963.2021.1890762 doi (DE-627)DOAJ099473720 (DE-599)DOAJfc2203001dc649d7a2ed576dc376bf11 DE-627 ger DE-627 rakwb eng RC666-701 Malwina M. Roszkowska-Chojecka verfasserin aut Role of chymase in blood pressure control, plasma and tissue angiotensin II, renal Haemodynamics, and excretion in spontaneously hypertensive rats 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Chymase generates angiotensin II (ANG II) independently of angiotensin-converting enzyme in tissues and it contributes to vascular remodeling and development of hypertension, however the exact mechanism of its action is unclear. Methods: Hence, the effects of chymase inhibition were examined in anesthetized spontaneously hypertensive rats (SHR) in two stages of the disease development, ie. pre-hypertensive (SHR7) and with established hypertension (SHR16). Chymostatin, a commercial chymase inhibitor, was infused intravenously alone or in subsequent groups co-infused with captopril. Results: Mean blood pressure (MBP), total renal blood flow (RBF) and ANG II content (plasma and tissues) were measured. In SHR16 chymase blockade significantly decreased MBP (−6%) and plasma (−38%), kidney (−71%) and heart (−52%) ANG II levels. In SHR7 chymostatin did not influence MBP or RBF, but significantly decreased heart ANG II level. Conclusion: Jointly, functional studies and ANG II determinations support the evidence that in SHR chymase can raise plasma ANG II and contribute to blood pressure elevation. We propose that addition of chymase blockade to ACE inhibition could be a promising approach in the treatment of hypertensive patients resistant to therapy with ACE-inhibitors alone. chymase chymostatin hypertension renin-angiotensin system angiotensin ii spontaneously hypertensive rats renal blood flow Diseases of the circulatory (Cardiovascular) system Iwona Baranowska verfasserin aut Olga Gawrys verfasserin aut Janusz Sadowski verfasserin aut Agnieszka Walkowska verfasserin aut Malgorzata Kalisz verfasserin aut Anna Litwiniuk verfasserin aut Elzbieta Kompanowska-Jezierska verfasserin aut In Clinical and Experimental Hypertension Taylor & Francis Group, 2023 43(2021), 5, Seite 392-401 (DE-627)323606504 (DE-600)2026245-0 15256006 nnns volume:43 year:2021 number:5 pages:392-401 https://doi.org/10.1080/10641963.2021.1890762 kostenfrei https://doaj.org/article/fc2203001dc649d7a2ed576dc376bf11 kostenfrei http://dx.doi.org/10.1080/10641963.2021.1890762 kostenfrei https://doaj.org/toc/1064-1963 Journal toc kostenfrei https://doaj.org/toc/1525-6006 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_206 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4305 GBV_ILN_4338 AR 43 2021 5 392-401 |
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10.1080/10641963.2021.1890762 doi (DE-627)DOAJ099473720 (DE-599)DOAJfc2203001dc649d7a2ed576dc376bf11 DE-627 ger DE-627 rakwb eng RC666-701 Malwina M. Roszkowska-Chojecka verfasserin aut Role of chymase in blood pressure control, plasma and tissue angiotensin II, renal Haemodynamics, and excretion in spontaneously hypertensive rats 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Chymase generates angiotensin II (ANG II) independently of angiotensin-converting enzyme in tissues and it contributes to vascular remodeling and development of hypertension, however the exact mechanism of its action is unclear. Methods: Hence, the effects of chymase inhibition were examined in anesthetized spontaneously hypertensive rats (SHR) in two stages of the disease development, ie. pre-hypertensive (SHR7) and with established hypertension (SHR16). Chymostatin, a commercial chymase inhibitor, was infused intravenously alone or in subsequent groups co-infused with captopril. Results: Mean blood pressure (MBP), total renal blood flow (RBF) and ANG II content (plasma and tissues) were measured. In SHR16 chymase blockade significantly decreased MBP (−6%) and plasma (−38%), kidney (−71%) and heart (−52%) ANG II levels. In SHR7 chymostatin did not influence MBP or RBF, but significantly decreased heart ANG II level. Conclusion: Jointly, functional studies and ANG II determinations support the evidence that in SHR chymase can raise plasma ANG II and contribute to blood pressure elevation. We propose that addition of chymase blockade to ACE inhibition could be a promising approach in the treatment of hypertensive patients resistant to therapy with ACE-inhibitors alone. chymase chymostatin hypertension renin-angiotensin system angiotensin ii spontaneously hypertensive rats renal blood flow Diseases of the circulatory (Cardiovascular) system Iwona Baranowska verfasserin aut Olga Gawrys verfasserin aut Janusz Sadowski verfasserin aut Agnieszka Walkowska verfasserin aut Malgorzata Kalisz verfasserin aut Anna Litwiniuk verfasserin aut Elzbieta Kompanowska-Jezierska verfasserin aut In Clinical and Experimental Hypertension Taylor & Francis Group, 2023 43(2021), 5, Seite 392-401 (DE-627)323606504 (DE-600)2026245-0 15256006 nnns volume:43 year:2021 number:5 pages:392-401 https://doi.org/10.1080/10641963.2021.1890762 kostenfrei https://doaj.org/article/fc2203001dc649d7a2ed576dc376bf11 kostenfrei http://dx.doi.org/10.1080/10641963.2021.1890762 kostenfrei https://doaj.org/toc/1064-1963 Journal toc kostenfrei https://doaj.org/toc/1525-6006 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_206 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4305 GBV_ILN_4338 AR 43 2021 5 392-401 |
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10.1080/10641963.2021.1890762 doi (DE-627)DOAJ099473720 (DE-599)DOAJfc2203001dc649d7a2ed576dc376bf11 DE-627 ger DE-627 rakwb eng RC666-701 Malwina M. Roszkowska-Chojecka verfasserin aut Role of chymase in blood pressure control, plasma and tissue angiotensin II, renal Haemodynamics, and excretion in spontaneously hypertensive rats 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Chymase generates angiotensin II (ANG II) independently of angiotensin-converting enzyme in tissues and it contributes to vascular remodeling and development of hypertension, however the exact mechanism of its action is unclear. Methods: Hence, the effects of chymase inhibition were examined in anesthetized spontaneously hypertensive rats (SHR) in two stages of the disease development, ie. pre-hypertensive (SHR7) and with established hypertension (SHR16). Chymostatin, a commercial chymase inhibitor, was infused intravenously alone or in subsequent groups co-infused with captopril. Results: Mean blood pressure (MBP), total renal blood flow (RBF) and ANG II content (plasma and tissues) were measured. In SHR16 chymase blockade significantly decreased MBP (−6%) and plasma (−38%), kidney (−71%) and heart (−52%) ANG II levels. In SHR7 chymostatin did not influence MBP or RBF, but significantly decreased heart ANG II level. Conclusion: Jointly, functional studies and ANG II determinations support the evidence that in SHR chymase can raise plasma ANG II and contribute to blood pressure elevation. We propose that addition of chymase blockade to ACE inhibition could be a promising approach in the treatment of hypertensive patients resistant to therapy with ACE-inhibitors alone. chymase chymostatin hypertension renin-angiotensin system angiotensin ii spontaneously hypertensive rats renal blood flow Diseases of the circulatory (Cardiovascular) system Iwona Baranowska verfasserin aut Olga Gawrys verfasserin aut Janusz Sadowski verfasserin aut Agnieszka Walkowska verfasserin aut Malgorzata Kalisz verfasserin aut Anna Litwiniuk verfasserin aut Elzbieta Kompanowska-Jezierska verfasserin aut In Clinical and Experimental Hypertension Taylor & Francis Group, 2023 43(2021), 5, Seite 392-401 (DE-627)323606504 (DE-600)2026245-0 15256006 nnns volume:43 year:2021 number:5 pages:392-401 https://doi.org/10.1080/10641963.2021.1890762 kostenfrei https://doaj.org/article/fc2203001dc649d7a2ed576dc376bf11 kostenfrei http://dx.doi.org/10.1080/10641963.2021.1890762 kostenfrei https://doaj.org/toc/1064-1963 Journal toc kostenfrei https://doaj.org/toc/1525-6006 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_206 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4305 GBV_ILN_4338 AR 43 2021 5 392-401 |
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10.1080/10641963.2021.1890762 doi (DE-627)DOAJ099473720 (DE-599)DOAJfc2203001dc649d7a2ed576dc376bf11 DE-627 ger DE-627 rakwb eng RC666-701 Malwina M. Roszkowska-Chojecka verfasserin aut Role of chymase in blood pressure control, plasma and tissue angiotensin II, renal Haemodynamics, and excretion in spontaneously hypertensive rats 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Chymase generates angiotensin II (ANG II) independently of angiotensin-converting enzyme in tissues and it contributes to vascular remodeling and development of hypertension, however the exact mechanism of its action is unclear. Methods: Hence, the effects of chymase inhibition were examined in anesthetized spontaneously hypertensive rats (SHR) in two stages of the disease development, ie. pre-hypertensive (SHR7) and with established hypertension (SHR16). Chymostatin, a commercial chymase inhibitor, was infused intravenously alone or in subsequent groups co-infused with captopril. Results: Mean blood pressure (MBP), total renal blood flow (RBF) and ANG II content (plasma and tissues) were measured. In SHR16 chymase blockade significantly decreased MBP (−6%) and plasma (−38%), kidney (−71%) and heart (−52%) ANG II levels. In SHR7 chymostatin did not influence MBP or RBF, but significantly decreased heart ANG II level. Conclusion: Jointly, functional studies and ANG II determinations support the evidence that in SHR chymase can raise plasma ANG II and contribute to blood pressure elevation. We propose that addition of chymase blockade to ACE inhibition could be a promising approach in the treatment of hypertensive patients resistant to therapy with ACE-inhibitors alone. chymase chymostatin hypertension renin-angiotensin system angiotensin ii spontaneously hypertensive rats renal blood flow Diseases of the circulatory (Cardiovascular) system Iwona Baranowska verfasserin aut Olga Gawrys verfasserin aut Janusz Sadowski verfasserin aut Agnieszka Walkowska verfasserin aut Malgorzata Kalisz verfasserin aut Anna Litwiniuk verfasserin aut Elzbieta Kompanowska-Jezierska verfasserin aut In Clinical and Experimental Hypertension Taylor & Francis Group, 2023 43(2021), 5, Seite 392-401 (DE-627)323606504 (DE-600)2026245-0 15256006 nnns volume:43 year:2021 number:5 pages:392-401 https://doi.org/10.1080/10641963.2021.1890762 kostenfrei https://doaj.org/article/fc2203001dc649d7a2ed576dc376bf11 kostenfrei http://dx.doi.org/10.1080/10641963.2021.1890762 kostenfrei https://doaj.org/toc/1064-1963 Journal toc kostenfrei https://doaj.org/toc/1525-6006 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_206 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4305 GBV_ILN_4338 AR 43 2021 5 392-401 |
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10.1080/10641963.2021.1890762 doi (DE-627)DOAJ099473720 (DE-599)DOAJfc2203001dc649d7a2ed576dc376bf11 DE-627 ger DE-627 rakwb eng RC666-701 Malwina M. Roszkowska-Chojecka verfasserin aut Role of chymase in blood pressure control, plasma and tissue angiotensin II, renal Haemodynamics, and excretion in spontaneously hypertensive rats 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Chymase generates angiotensin II (ANG II) independently of angiotensin-converting enzyme in tissues and it contributes to vascular remodeling and development of hypertension, however the exact mechanism of its action is unclear. Methods: Hence, the effects of chymase inhibition were examined in anesthetized spontaneously hypertensive rats (SHR) in two stages of the disease development, ie. pre-hypertensive (SHR7) and with established hypertension (SHR16). Chymostatin, a commercial chymase inhibitor, was infused intravenously alone or in subsequent groups co-infused with captopril. Results: Mean blood pressure (MBP), total renal blood flow (RBF) and ANG II content (plasma and tissues) were measured. In SHR16 chymase blockade significantly decreased MBP (−6%) and plasma (−38%), kidney (−71%) and heart (−52%) ANG II levels. In SHR7 chymostatin did not influence MBP or RBF, but significantly decreased heart ANG II level. Conclusion: Jointly, functional studies and ANG II determinations support the evidence that in SHR chymase can raise plasma ANG II and contribute to blood pressure elevation. We propose that addition of chymase blockade to ACE inhibition could be a promising approach in the treatment of hypertensive patients resistant to therapy with ACE-inhibitors alone. chymase chymostatin hypertension renin-angiotensin system angiotensin ii spontaneously hypertensive rats renal blood flow Diseases of the circulatory (Cardiovascular) system Iwona Baranowska verfasserin aut Olga Gawrys verfasserin aut Janusz Sadowski verfasserin aut Agnieszka Walkowska verfasserin aut Malgorzata Kalisz verfasserin aut Anna Litwiniuk verfasserin aut Elzbieta Kompanowska-Jezierska verfasserin aut In Clinical and Experimental Hypertension Taylor & Francis Group, 2023 43(2021), 5, Seite 392-401 (DE-627)323606504 (DE-600)2026245-0 15256006 nnns volume:43 year:2021 number:5 pages:392-401 https://doi.org/10.1080/10641963.2021.1890762 kostenfrei https://doaj.org/article/fc2203001dc649d7a2ed576dc376bf11 kostenfrei http://dx.doi.org/10.1080/10641963.2021.1890762 kostenfrei https://doaj.org/toc/1064-1963 Journal toc kostenfrei https://doaj.org/toc/1525-6006 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_206 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4305 GBV_ILN_4338 AR 43 2021 5 392-401 |
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Roszkowska-Chojecka</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Role of chymase in blood pressure control, plasma and tissue angiotensin II, renal Haemodynamics, and excretion in spontaneously hypertensive rats</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2021</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background: Chymase generates angiotensin II (ANG II) independently of angiotensin-converting enzyme in tissues and it contributes to vascular remodeling and development of hypertension, however the exact mechanism of its action is unclear. 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RC666-701 Role of chymase in blood pressure control, plasma and tissue angiotensin II, renal Haemodynamics, and excretion in spontaneously hypertensive rats chymase chymostatin hypertension renin-angiotensin system angiotensin ii spontaneously hypertensive rats renal blood flow |
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Malwina M. Roszkowska-Chojecka Iwona Baranowska Olga Gawrys Janusz Sadowski Agnieszka Walkowska Malgorzata Kalisz Anna Litwiniuk Elzbieta Kompanowska-Jezierska |
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role of chymase in blood pressure control, plasma and tissue angiotensin ii, renal haemodynamics, and excretion in spontaneously hypertensive rats |
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Role of chymase in blood pressure control, plasma and tissue angiotensin II, renal Haemodynamics, and excretion in spontaneously hypertensive rats |
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Background: Chymase generates angiotensin II (ANG II) independently of angiotensin-converting enzyme in tissues and it contributes to vascular remodeling and development of hypertension, however the exact mechanism of its action is unclear. Methods: Hence, the effects of chymase inhibition were examined in anesthetized spontaneously hypertensive rats (SHR) in two stages of the disease development, ie. pre-hypertensive (SHR7) and with established hypertension (SHR16). Chymostatin, a commercial chymase inhibitor, was infused intravenously alone or in subsequent groups co-infused with captopril. Results: Mean blood pressure (MBP), total renal blood flow (RBF) and ANG II content (plasma and tissues) were measured. In SHR16 chymase blockade significantly decreased MBP (−6%) and plasma (−38%), kidney (−71%) and heart (−52%) ANG II levels. In SHR7 chymostatin did not influence MBP or RBF, but significantly decreased heart ANG II level. Conclusion: Jointly, functional studies and ANG II determinations support the evidence that in SHR chymase can raise plasma ANG II and contribute to blood pressure elevation. We propose that addition of chymase blockade to ACE inhibition could be a promising approach in the treatment of hypertensive patients resistant to therapy with ACE-inhibitors alone. |
abstractGer |
Background: Chymase generates angiotensin II (ANG II) independently of angiotensin-converting enzyme in tissues and it contributes to vascular remodeling and development of hypertension, however the exact mechanism of its action is unclear. Methods: Hence, the effects of chymase inhibition were examined in anesthetized spontaneously hypertensive rats (SHR) in two stages of the disease development, ie. pre-hypertensive (SHR7) and with established hypertension (SHR16). Chymostatin, a commercial chymase inhibitor, was infused intravenously alone or in subsequent groups co-infused with captopril. Results: Mean blood pressure (MBP), total renal blood flow (RBF) and ANG II content (plasma and tissues) were measured. In SHR16 chymase blockade significantly decreased MBP (−6%) and plasma (−38%), kidney (−71%) and heart (−52%) ANG II levels. In SHR7 chymostatin did not influence MBP or RBF, but significantly decreased heart ANG II level. Conclusion: Jointly, functional studies and ANG II determinations support the evidence that in SHR chymase can raise plasma ANG II and contribute to blood pressure elevation. We propose that addition of chymase blockade to ACE inhibition could be a promising approach in the treatment of hypertensive patients resistant to therapy with ACE-inhibitors alone. |
abstract_unstemmed |
Background: Chymase generates angiotensin II (ANG II) independently of angiotensin-converting enzyme in tissues and it contributes to vascular remodeling and development of hypertension, however the exact mechanism of its action is unclear. Methods: Hence, the effects of chymase inhibition were examined in anesthetized spontaneously hypertensive rats (SHR) in two stages of the disease development, ie. pre-hypertensive (SHR7) and with established hypertension (SHR16). Chymostatin, a commercial chymase inhibitor, was infused intravenously alone or in subsequent groups co-infused with captopril. Results: Mean blood pressure (MBP), total renal blood flow (RBF) and ANG II content (plasma and tissues) were measured. In SHR16 chymase blockade significantly decreased MBP (−6%) and plasma (−38%), kidney (−71%) and heart (−52%) ANG II levels. In SHR7 chymostatin did not influence MBP or RBF, but significantly decreased heart ANG II level. Conclusion: Jointly, functional studies and ANG II determinations support the evidence that in SHR chymase can raise plasma ANG II and contribute to blood pressure elevation. We propose that addition of chymase blockade to ACE inhibition could be a promising approach in the treatment of hypertensive patients resistant to therapy with ACE-inhibitors alone. |
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