Angiotensin II induced cerebral microvascular inflammation and increased blood–brain barrier permeability via oxidative stress
Abstract Although hypertension has been implicated in the pathogenesis of vascular disease, its role in inflammatory responses, especially in brain, remains unclear. In this study we found key mechanisms by which angiotensin II (AngII) mediates cerebral microvascular inflammation. C57BL/6 male mice...
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| Veröffentlicht in: | Neuroscience 2010-12, Vol.171 (3), p.852-858 |
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| description | Abstract Although hypertension has been implicated in the pathogenesis of vascular disease, its role in inflammatory responses, especially in brain, remains unclear. In this study we found key mechanisms by which angiotensin II (AngII) mediates cerebral microvascular inflammation. C57BL/6 male mice were subjected to slow-pressor dose of AngII infusion using osmotic mini-pumps at a rate of 400 ng/kg/min for 14 days. Vascular inflammation in the brain was evaluated by analysis of leukocyte–endothelial interaction and blood–brain barrier (BBB) permeability. Results from intravital microscopy of pial vessels in vivo , revealed a 4.2 fold ( P |
| doi_str_mv | 10.1016/j.neuroscience.2010.09.029 |
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In this study we found key mechanisms by which angiotensin II (AngII) mediates cerebral microvascular inflammation. C57BL/6 male mice were subjected to slow-pressor dose of AngII infusion using osmotic mini-pumps at a rate of 400 ng/kg/min for 14 days. Vascular inflammation in the brain was evaluated by analysis of leukocyte–endothelial interaction and blood–brain barrier (BBB) permeability. Results from intravital microscopy of pial vessels in vivo , revealed a 4.2 fold ( P <0.05, compared to vehicle) increase in leukocyte adhesion on day 4 of AngII infusion. This effect persisted through day 14 of AngII infusion, which resulted in a 2.6 fold ( P <0.01, compared to vehicle) increase in leukocyte adhesion. Furthermore, evaluation of BBB permeability by Evans Blue extravasation showed that Ang II significantly affected the BBB, inducing 3.8 times ( P <0.05, compared to vehicle) higher permeability. Previously we reported that AngII mediated hypertension promotes oxidative stress in the vasculature. Thus, we used the superoxide scavenger; 4-hydroxy-TEMPO (Tempol) to determine whether AngII via oxidative stress could contribute to higher leukocyte adhesion and increased BBB permeability. Tempol was given via drinking water (2 mmol) on day 4th following Ang II infusion, since oxidative stress increases in this model on day 4. Treatment with Tempol significantly attenuated the increased leukocyte/endothelial interactions and protected the BBB integrity on day 14 of AngII infusion. In conclusion, AngII via oxidative stress increases cerebral microvasculature inflammation and leads to greater immune-endothelial interaction and higher BBB permeability. This finding may open new avenues for the management of nervous system pathology involving cerebrovascular inflammation.</description><identifier>ISSN: 0306-4522</identifier><identifier>EISSN: 1873-7544</identifier><identifier>DOI: 10.1016/j.neuroscience.2010.09.029</identifier><identifier>PMID: 20870012</identifier><identifier>CODEN: NRSCDN</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>angiotensin II ; Angiotensin II - administration & dosage ; Angiotensin II - toxicity ; Animals ; Biological and medical sciences ; Blood-Brain Barrier - drug effects ; Blood-Brain Barrier - metabolism ; Blood-Brain Barrier - pathology ; blood–brain barrier ; Cerebral Arteries - drug effects ; Cerebral Arteries - metabolism ; Cerebral Arteries - pathology ; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges ; cerebrovascular ; Drug Administration Schedule ; Fundamental and applied biological sciences. Psychology ; hypertension ; inflammation ; Inflammation Mediators - administration & dosage ; Inflammation Mediators - toxicity ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Microcirculation - drug effects ; Microcirculation - physiology ; Microvessels - drug effects ; Microvessels - metabolism ; Microvessels - pathology ; Neurology ; oxidative stress ; Oxidative Stress - drug effects ; Oxidative Stress - physiology ; Permeability - drug effects ; Vertebrates: nervous system and sense organs</subject><ispartof>Neuroscience, 2010-12, Vol.171 (3), p.852-858</ispartof><rights>IBRO</rights><rights>2010 IBRO</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c496t-cefa2a3d5521d04cdc8309fe0e31a4637b10b646c357d937fdeb500ba0e9e8343</citedby><cites>FETCH-LOGICAL-c496t-cefa2a3d5521d04cdc8309fe0e31a4637b10b646c357d937fdeb500ba0e9e8343</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.neuroscience.2010.09.029$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3541,27915,27916,45986</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23504673$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20870012$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, M</creatorcontrib><creatorcontrib>Mao, Y</creatorcontrib><creatorcontrib>Ramirez, S.H</creatorcontrib><creatorcontrib>Tuma, R.F</creatorcontrib><creatorcontrib>Chabrashvili, T</creatorcontrib><title>Angiotensin II induced cerebral microvascular inflammation and increased blood–brain barrier permeability via oxidative stress</title><title>Neuroscience</title><addtitle>Neuroscience</addtitle><description>Abstract Although hypertension has been implicated in the pathogenesis of vascular disease, its role in inflammatory responses, especially in brain, remains unclear. In this study we found key mechanisms by which angiotensin II (AngII) mediates cerebral microvascular inflammation. C57BL/6 male mice were subjected to slow-pressor dose of AngII infusion using osmotic mini-pumps at a rate of 400 ng/kg/min for 14 days. Vascular inflammation in the brain was evaluated by analysis of leukocyte–endothelial interaction and blood–brain barrier (BBB) permeability. Results from intravital microscopy of pial vessels in vivo , revealed a 4.2 fold ( P <0.05, compared to vehicle) increase in leukocyte adhesion on day 4 of AngII infusion. This effect persisted through day 14 of AngII infusion, which resulted in a 2.6 fold ( P <0.01, compared to vehicle) increase in leukocyte adhesion. Furthermore, evaluation of BBB permeability by Evans Blue extravasation showed that Ang II significantly affected the BBB, inducing 3.8 times ( P <0.05, compared to vehicle) higher permeability. Previously we reported that AngII mediated hypertension promotes oxidative stress in the vasculature. Thus, we used the superoxide scavenger; 4-hydroxy-TEMPO (Tempol) to determine whether AngII via oxidative stress could contribute to higher leukocyte adhesion and increased BBB permeability. Tempol was given via drinking water (2 mmol) on day 4th following Ang II infusion, since oxidative stress increases in this model on day 4. Treatment with Tempol significantly attenuated the increased leukocyte/endothelial interactions and protected the BBB integrity on day 14 of AngII infusion. In conclusion, AngII via oxidative stress increases cerebral microvasculature inflammation and leads to greater immune-endothelial interaction and higher BBB permeability. This finding may open new avenues for the management of nervous system pathology involving cerebrovascular inflammation.</description><subject>angiotensin II</subject><subject>Angiotensin II - administration & dosage</subject><subject>Angiotensin II - toxicity</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood-Brain Barrier - drug effects</subject><subject>Blood-Brain Barrier - metabolism</subject><subject>Blood-Brain Barrier - pathology</subject><subject>blood–brain barrier</subject><subject>Cerebral Arteries - drug effects</subject><subject>Cerebral Arteries - metabolism</subject><subject>Cerebral Arteries - pathology</subject><subject>Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges</subject><subject>cerebrovascular</subject><subject>Drug Administration Schedule</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>hypertension</subject><subject>inflammation</subject><subject>Inflammation Mediators - administration & dosage</subject><subject>Inflammation Mediators - toxicity</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Microcirculation - drug effects</subject><subject>Microcirculation - physiology</subject><subject>Microvessels - drug effects</subject><subject>Microvessels - metabolism</subject><subject>Microvessels - pathology</subject><subject>Neurology</subject><subject>oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Oxidative Stress - physiology</subject><subject>Permeability - drug effects</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0306-4522</issn><issn>1873-7544</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks-KFDEQxoMo7uzqK0gjiKceK52k0-1BWFZXBxY8qOeQTqolY3cyJt3Dzm3fwTf0SUwz4x-8aC6B1O-rKr4vhDylsKZA6xfbtcc5hmQceoPrCnIB2jVU7T2yoo1kpRSc3ycrYFCXXFTVGTlPaQv5CM4ekrMKGglAqxW5u_SfXZjQJ-eLzaZw3s4GbWEwYhf1UIzOxLDXycyDjrncD3oc9eSCL7S3-cFE1CkruiEE-_3uW1blVp2O0WEsdhhH1J0b3HQo9k4X4dbZLN9jkaaIKT0iD3o9JHx8ui_Ip-s3H6_elTfv326uLm9Kw9t6Kg32utLMClFRC9xY0zBoewRkVPOayY5CV_PaMCFty2RvsRMAnQZssWGcXZDnx767GL7OmCY1umRwGLTHMCfViFqKtmnqf5PQ8JpWvMnkyyOZLUopYq920Y06HhQFtUSlturPqNQSlYJW5aiy-MlpzNyNaH9Jf2aTgWcnILuvhz5qb1z6zTEBvJYsc6-PHGb79tl0dRpnXUQzKRvc_-3z6q82ZnDe5clf8IBpG-boc0CKqlQpUB-Wz7X8LbosK6VkPwApotHY</recordid><startdate>20101215</startdate><enddate>20101215</enddate><creator>Zhang, M</creator><creator>Mao, Y</creator><creator>Ramirez, S.H</creator><creator>Tuma, R.F</creator><creator>Chabrashvili, T</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TK</scope></search><sort><creationdate>20101215</creationdate><title>Angiotensin II induced cerebral microvascular inflammation and increased blood–brain barrier permeability via oxidative stress</title><author>Zhang, M ; Mao, Y ; Ramirez, S.H ; Tuma, R.F ; Chabrashvili, T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c496t-cefa2a3d5521d04cdc8309fe0e31a4637b10b646c357d937fdeb500ba0e9e8343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>angiotensin II</topic><topic>Angiotensin II - administration & dosage</topic><topic>Angiotensin II - toxicity</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood-Brain Barrier - drug effects</topic><topic>Blood-Brain Barrier - metabolism</topic><topic>Blood-Brain Barrier - pathology</topic><topic>blood–brain barrier</topic><topic>Cerebral Arteries - drug effects</topic><topic>Cerebral Arteries - metabolism</topic><topic>Cerebral Arteries - pathology</topic><topic>Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges</topic><topic>cerebrovascular</topic><topic>Drug Administration Schedule</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>hypertension</topic><topic>inflammation</topic><topic>Inflammation Mediators - administration & dosage</topic><topic>Inflammation Mediators - toxicity</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Microcirculation - drug effects</topic><topic>Microcirculation - physiology</topic><topic>Microvessels - drug effects</topic><topic>Microvessels - metabolism</topic><topic>Microvessels - pathology</topic><topic>Neurology</topic><topic>oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Oxidative Stress - physiology</topic><topic>Permeability - drug effects</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, M</creatorcontrib><creatorcontrib>Mao, Y</creatorcontrib><creatorcontrib>Ramirez, S.H</creatorcontrib><creatorcontrib>Tuma, R.F</creatorcontrib><creatorcontrib>Chabrashvili, T</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><jtitle>Neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, M</au><au>Mao, Y</au><au>Ramirez, S.H</au><au>Tuma, R.F</au><au>Chabrashvili, T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Angiotensin II induced cerebral microvascular inflammation and increased blood–brain barrier permeability via oxidative stress</atitle><jtitle>Neuroscience</jtitle><addtitle>Neuroscience</addtitle><date>2010-12-15</date><risdate>2010</risdate><volume>171</volume><issue>3</issue><spage>852</spage><epage>858</epage><pages>852-858</pages><issn>0306-4522</issn><eissn>1873-7544</eissn><coden>NRSCDN</coden><abstract>Abstract Although hypertension has been implicated in the pathogenesis of vascular disease, its role in inflammatory responses, especially in brain, remains unclear. In this study we found key mechanisms by which angiotensin II (AngII) mediates cerebral microvascular inflammation. C57BL/6 male mice were subjected to slow-pressor dose of AngII infusion using osmotic mini-pumps at a rate of 400 ng/kg/min for 14 days. Vascular inflammation in the brain was evaluated by analysis of leukocyte–endothelial interaction and blood–brain barrier (BBB) permeability. Results from intravital microscopy of pial vessels in vivo , revealed a 4.2 fold ( P <0.05, compared to vehicle) increase in leukocyte adhesion on day 4 of AngII infusion. This effect persisted through day 14 of AngII infusion, which resulted in a 2.6 fold ( P <0.01, compared to vehicle) increase in leukocyte adhesion. Furthermore, evaluation of BBB permeability by Evans Blue extravasation showed that Ang II significantly affected the BBB, inducing 3.8 times ( P <0.05, compared to vehicle) higher permeability. Previously we reported that AngII mediated hypertension promotes oxidative stress in the vasculature. Thus, we used the superoxide scavenger; 4-hydroxy-TEMPO (Tempol) to determine whether AngII via oxidative stress could contribute to higher leukocyte adhesion and increased BBB permeability. Tempol was given via drinking water (2 mmol) on day 4th following Ang II infusion, since oxidative stress increases in this model on day 4. Treatment with Tempol significantly attenuated the increased leukocyte/endothelial interactions and protected the BBB integrity on day 14 of AngII infusion. In conclusion, AngII via oxidative stress increases cerebral microvasculature inflammation and leads to greater immune-endothelial interaction and higher BBB permeability. This finding may open new avenues for the management of nervous system pathology involving cerebrovascular inflammation.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>20870012</pmid><doi>10.1016/j.neuroscience.2010.09.029</doi><tpages>7</tpages></addata></record> |
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| subjects | angiotensin II Angiotensin II - administration & dosage Angiotensin II - toxicity Animals Biological and medical sciences Blood-Brain Barrier - drug effects Blood-Brain Barrier - metabolism Blood-Brain Barrier - pathology blood–brain barrier Cerebral Arteries - drug effects Cerebral Arteries - metabolism Cerebral Arteries - pathology Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges cerebrovascular Drug Administration Schedule Fundamental and applied biological sciences. Psychology hypertension inflammation Inflammation Mediators - administration & dosage Inflammation Mediators - toxicity Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Microcirculation - drug effects Microcirculation - physiology Microvessels - drug effects Microvessels - metabolism Microvessels - pathology Neurology oxidative stress Oxidative Stress - drug effects Oxidative Stress - physiology Permeability - drug effects Vertebrates: nervous system and sense organs |
| title | Angiotensin II induced cerebral microvascular inflammation and increased blood–brain barrier permeability via oxidative stress |
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