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Impaired endothelium-dependent responses and enhanced influence of rho-kinase in cerebral arterioles in type II diabetes
Although the incidence of type II diabetes is increasing, very little is known regarding vascular responses in the cerebral circulation in this disease. The goals of this study were to examine the role of superoxide in impaired endothelium-dependent responses and to examine the influence of Rho-kina...
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| Published in: | Stroke (1970) 2005-02, Vol.36 (2), p.342-347 |
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| container_end_page | 347 |
| container_issue | 2 |
| container_start_page | 342 |
| container_title | Stroke (1970) |
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| creator | DIDION, Sean P LYNCH, Cynthia M BAUMBACH, Gary L FARACI, Frank M |
| description | Although the incidence of type II diabetes is increasing, very little is known regarding vascular responses in the cerebral circulation in this disease. The goals of this study were to examine the role of superoxide in impaired endothelium-dependent responses and to examine the influence of Rho-kinase on vascular tone in the cerebral microcirculation in type II diabetes.
Diameter of cerebral arterioles (29+/-1 microm; mean+/-SE) was measured in vivo using a cranial window in anesthetized db/db and control mice.
Dilatation of cerebral arterioles in response to acetylcholine (ACh; 1 and 10 micromol/L), but not to nitroprusside, was markedly reduced in db/db mice (eg, 10 micromol/L ACh produced 29+/-1% and 9+/-1% in control and db/db mice, respectively). Superoxide levels were increased (P |
| doi_str_mv | 10.1161/01.STR.0000152952.42730.92 |
| format | article |
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Diameter of cerebral arterioles (29+/-1 microm; mean+/-SE) was measured in vivo using a cranial window in anesthetized db/db and control mice.
Dilatation of cerebral arterioles in response to acetylcholine (ACh; 1 and 10 micromol/L), but not to nitroprusside, was markedly reduced in db/db mice (eg, 10 micromol/L ACh produced 29+/-1% and 9+/-1% in control and db/db mice, respectively). Superoxide levels were increased (P<0.05) in cerebral arterioles from db/db mice (n=6) compared with controls (n=6). Vasodilatation to ACh in db/db mice was restored to normal by polyethylene glycol-superoxide dismutase (100 U/mL). Y-27632 (1 to 100 micromol/L; a Rho-kinase inhibitor) produced modest vasodilatation in control mice but much greater responses in db/db mice. N(G)-nitro-L-arginine (100 micromol/L; an inhibitor of NO synthase) significantly enhanced Y-27632-induced dilatation in control mice to similar levels as observed in db/db mice.
These findings provide the first evidence for superoxide-mediated impairment of endothelium-dependent responses of cerebral vessels in any model of type II diabetes. In addition, the influence of Rho-kinase on resting tone appears to be selectively enhanced in the cerebral microcirculation in this genetic model of type II diabetes.</description><identifier>ISSN: 0039-2499</identifier><identifier>EISSN: 1524-4628</identifier><identifier>DOI: 10.1161/01.STR.0000152952.42730.92</identifier><identifier>PMID: 15637328</identifier><identifier>CODEN: SJCCA7</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Acetylcholine - pharmacology ; Amides - pharmacology ; Animals ; Biological and medical sciences ; Blood Glucose - metabolism ; Body Weight ; Cerebral Arteries - pathology ; Cerebrovascular Circulation ; Diabetes Mellitus, Type 2 - pathology ; Endothelium, Vascular - metabolism ; Endothelium, Vascular - pathology ; Enzyme Inhibitors - pharmacology ; Errors of metabolism ; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy ; Intracellular Signaling Peptides and Proteins ; Lipids (lysosomal enzyme disorders, storage diseases) ; Medical sciences ; Metabolic diseases ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microscopy, Confocal ; Nervous system (semeiology, syndromes) ; Neurology ; Nitric Oxide Synthase - chemistry ; Nitroarginine - chemistry ; Nitroarginine - pharmacology ; Nitroprusside - pharmacology ; Polyethylene Glycols - metabolism ; Protein-Serine-Threonine Kinases - physiology ; Pyridines - pharmacology ; Reactive Oxygen Species ; rho-Associated Kinases ; Superoxide Dismutase - metabolism ; Superoxides - chemistry ; Superoxides - metabolism ; Vascular diseases and vascular malformations of the nervous system ; Vasoconstrictor Agents - pharmacology ; Vasodilation ; Vasodilator Agents - pharmacology</subject><ispartof>Stroke (1970), 2005-02, Vol.36 (2), p.342-347</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c588t-49904a6e56a0a4c77d649068e707a06d9da0351b7e61540666ae3cbe389cde193</citedby><cites>FETCH-LOGICAL-c588t-49904a6e56a0a4c77d649068e707a06d9da0351b7e61540666ae3cbe389cde193</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16449627$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15637328$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>DIDION, Sean P</creatorcontrib><creatorcontrib>LYNCH, Cynthia M</creatorcontrib><creatorcontrib>BAUMBACH, Gary L</creatorcontrib><creatorcontrib>FARACI, Frank M</creatorcontrib><title>Impaired endothelium-dependent responses and enhanced influence of rho-kinase in cerebral arterioles in type II diabetes</title><title>Stroke (1970)</title><addtitle>Stroke</addtitle><description>Although the incidence of type II diabetes is increasing, very little is known regarding vascular responses in the cerebral circulation in this disease. The goals of this study were to examine the role of superoxide in impaired endothelium-dependent responses and to examine the influence of Rho-kinase on vascular tone in the cerebral microcirculation in type II diabetes.
Diameter of cerebral arterioles (29+/-1 microm; mean+/-SE) was measured in vivo using a cranial window in anesthetized db/db and control mice.
Dilatation of cerebral arterioles in response to acetylcholine (ACh; 1 and 10 micromol/L), but not to nitroprusside, was markedly reduced in db/db mice (eg, 10 micromol/L ACh produced 29+/-1% and 9+/-1% in control and db/db mice, respectively). Superoxide levels were increased (P<0.05) in cerebral arterioles from db/db mice (n=6) compared with controls (n=6). Vasodilatation to ACh in db/db mice was restored to normal by polyethylene glycol-superoxide dismutase (100 U/mL). Y-27632 (1 to 100 micromol/L; a Rho-kinase inhibitor) produced modest vasodilatation in control mice but much greater responses in db/db mice. N(G)-nitro-L-arginine (100 micromol/L; an inhibitor of NO synthase) significantly enhanced Y-27632-induced dilatation in control mice to similar levels as observed in db/db mice.
These findings provide the first evidence for superoxide-mediated impairment of endothelium-dependent responses of cerebral vessels in any model of type II diabetes. In addition, the influence of Rho-kinase on resting tone appears to be selectively enhanced in the cerebral microcirculation in this genetic model of type II diabetes.</description><subject>Acetylcholine - pharmacology</subject><subject>Amides - pharmacology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood Glucose - metabolism</subject><subject>Body Weight</subject><subject>Cerebral Arteries - pathology</subject><subject>Cerebrovascular Circulation</subject><subject>Diabetes Mellitus, Type 2 - pathology</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Endothelium, Vascular - pathology</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Errors of metabolism</subject><subject>Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>Lipids (lysosomal enzyme disorders, storage diseases)</subject><subject>Medical sciences</subject><subject>Metabolic diseases</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Microscopy, Confocal</subject><subject>Nervous system (semeiology, syndromes)</subject><subject>Neurology</subject><subject>Nitric Oxide Synthase - chemistry</subject><subject>Nitroarginine - chemistry</subject><subject>Nitroarginine - pharmacology</subject><subject>Nitroprusside - pharmacology</subject><subject>Polyethylene Glycols - metabolism</subject><subject>Protein-Serine-Threonine Kinases - physiology</subject><subject>Pyridines - pharmacology</subject><subject>Reactive Oxygen Species</subject><subject>rho-Associated Kinases</subject><subject>Superoxide Dismutase - metabolism</subject><subject>Superoxides - chemistry</subject><subject>Superoxides - metabolism</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><subject>Vasoconstrictor Agents - pharmacology</subject><subject>Vasodilation</subject><subject>Vasodilator Agents - pharmacology</subject><issn>0039-2499</issn><issn>1524-4628</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNqFkV1rFTEQhoMo7WntX5Ag6N2u-c7GOylaDxQEW6_D7GaWE90vk11o_31Te-BcmptkXp53ZshLyHvOas4N_8R4fXf_s2blcC2cFrUSVrLaiVdkVxRVKSOa12THmHSVUM6dk4ucfxdeyEafkXOujbRSNDvysB8XiAkDxSnM6wGHuI1VwKWUOK00YV7mKWOmMD0zB5i6AsepHzYsTzr3NB3m6k-cIGPRaYcJ2wQDhbRiivNQvEVeHxek-z0NEVpcMb8lb3oYMl4d70vy69vX--vv1e2Pm_31l9uq002zVmV5psCgNsBAddYGoxwzDVpmgZngAjCpeWvRcK2YMQZQdi3KxnUBuZOX5ONL3yXNfzfMqx9j7nAYYMJ5y95Y2Qhu1X9B7qwwTugCfn4BuzTnnLD3S4ojpEfPmX8OyDPuS0D-FJD_F5B3opjfHads7YjhZD0mUoAPRwByB0OfyofHfOKMUs6Ubk_y9pqN</recordid><startdate>20050201</startdate><enddate>20050201</enddate><creator>DIDION, Sean P</creator><creator>LYNCH, Cynthia M</creator><creator>BAUMBACH, Gary L</creator><creator>FARACI, Frank M</creator><general>Lippincott Williams & Wilkins</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>7TK</scope><scope>7X8</scope></search><sort><creationdate>20050201</creationdate><title>Impaired endothelium-dependent responses and enhanced influence of rho-kinase in cerebral arterioles in type II diabetes</title><author>DIDION, Sean P ; LYNCH, Cynthia M ; BAUMBACH, Gary L ; FARACI, Frank M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c588t-49904a6e56a0a4c77d649068e707a06d9da0351b7e61540666ae3cbe389cde193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Acetylcholine - pharmacology</topic><topic>Amides - pharmacology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood Glucose - metabolism</topic><topic>Body Weight</topic><topic>Cerebral Arteries - pathology</topic><topic>Cerebrovascular Circulation</topic><topic>Diabetes Mellitus, Type 2 - pathology</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Endothelium, Vascular - pathology</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Errors of metabolism</topic><topic>Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>Lipids (lysosomal enzyme disorders, storage diseases)</topic><topic>Medical sciences</topic><topic>Metabolic diseases</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Microscopy, Confocal</topic><topic>Nervous system (semeiology, syndromes)</topic><topic>Neurology</topic><topic>Nitric Oxide Synthase - chemistry</topic><topic>Nitroarginine - chemistry</topic><topic>Nitroarginine - pharmacology</topic><topic>Nitroprusside - pharmacology</topic><topic>Polyethylene Glycols - metabolism</topic><topic>Protein-Serine-Threonine Kinases - physiology</topic><topic>Pyridines - pharmacology</topic><topic>Reactive Oxygen Species</topic><topic>rho-Associated Kinases</topic><topic>Superoxide Dismutase - metabolism</topic><topic>Superoxides - chemistry</topic><topic>Superoxides - metabolism</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><topic>Vasoconstrictor Agents - pharmacology</topic><topic>Vasodilation</topic><topic>Vasodilator Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>DIDION, Sean P</creatorcontrib><creatorcontrib>LYNCH, Cynthia M</creatorcontrib><creatorcontrib>BAUMBACH, Gary L</creatorcontrib><creatorcontrib>FARACI, Frank M</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>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Stroke (1970)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>DIDION, Sean P</au><au>LYNCH, Cynthia M</au><au>BAUMBACH, Gary L</au><au>FARACI, Frank M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impaired endothelium-dependent responses and enhanced influence of rho-kinase in cerebral arterioles in type II diabetes</atitle><jtitle>Stroke (1970)</jtitle><addtitle>Stroke</addtitle><date>2005-02-01</date><risdate>2005</risdate><volume>36</volume><issue>2</issue><spage>342</spage><epage>347</epage><pages>342-347</pages><issn>0039-2499</issn><eissn>1524-4628</eissn><coden>SJCCA7</coden><abstract>Although the incidence of type II diabetes is increasing, very little is known regarding vascular responses in the cerebral circulation in this disease. The goals of this study were to examine the role of superoxide in impaired endothelium-dependent responses and to examine the influence of Rho-kinase on vascular tone in the cerebral microcirculation in type II diabetes.
Diameter of cerebral arterioles (29+/-1 microm; mean+/-SE) was measured in vivo using a cranial window in anesthetized db/db and control mice.
Dilatation of cerebral arterioles in response to acetylcholine (ACh; 1 and 10 micromol/L), but not to nitroprusside, was markedly reduced in db/db mice (eg, 10 micromol/L ACh produced 29+/-1% and 9+/-1% in control and db/db mice, respectively). Superoxide levels were increased (P<0.05) in cerebral arterioles from db/db mice (n=6) compared with controls (n=6). Vasodilatation to ACh in db/db mice was restored to normal by polyethylene glycol-superoxide dismutase (100 U/mL). Y-27632 (1 to 100 micromol/L; a Rho-kinase inhibitor) produced modest vasodilatation in control mice but much greater responses in db/db mice. N(G)-nitro-L-arginine (100 micromol/L; an inhibitor of NO synthase) significantly enhanced Y-27632-induced dilatation in control mice to similar levels as observed in db/db mice.
These findings provide the first evidence for superoxide-mediated impairment of endothelium-dependent responses of cerebral vessels in any model of type II diabetes. In addition, the influence of Rho-kinase on resting tone appears to be selectively enhanced in the cerebral microcirculation in this genetic model of type II diabetes.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>15637328</pmid><doi>10.1161/01.STR.0000152952.42730.92</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acetylcholine - pharmacology Amides - pharmacology Animals Biological and medical sciences Blood Glucose - metabolism Body Weight Cerebral Arteries - pathology Cerebrovascular Circulation Diabetes Mellitus, Type 2 - pathology Endothelium, Vascular - metabolism Endothelium, Vascular - pathology Enzyme Inhibitors - pharmacology Errors of metabolism Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy Intracellular Signaling Peptides and Proteins Lipids (lysosomal enzyme disorders, storage diseases) Medical sciences Metabolic diseases Mice Mice, Inbred C57BL Mice, Transgenic Microscopy, Confocal Nervous system (semeiology, syndromes) Neurology Nitric Oxide Synthase - chemistry Nitroarginine - chemistry Nitroarginine - pharmacology Nitroprusside - pharmacology Polyethylene Glycols - metabolism Protein-Serine-Threonine Kinases - physiology Pyridines - pharmacology Reactive Oxygen Species rho-Associated Kinases Superoxide Dismutase - metabolism Superoxides - chemistry Superoxides - metabolism Vascular diseases and vascular malformations of the nervous system Vasoconstrictor Agents - pharmacology Vasodilation Vasodilator Agents - pharmacology |
| title | Impaired endothelium-dependent responses and enhanced influence of rho-kinase in cerebral arterioles in type II diabetes |
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