Production of 20-HETE and Its Role in Autoregulation of Cerebral Blood Flow
In the brain, pressure-induced myogenic constriction of cerebral arteriolar muscle contributes to autoregulation of cerebral blood flow (CBF). This study examined the role of 20-HETE in autoregulation of CBF in anesthetized rats. The expression of P-450 4A protein and mRNA was localized in isolated...
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| Veröffentlicht in: | Circulation research 2000-07, Vol.87 (1), p.60-65 |
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| creator | Gebremedhin, Debebe Lange, Andrew R Lowry, Timothy F Taheri, M Reza Birks, Eric K Hudetz, Antal G Narayanan, Jayashree Falck, John R Okamoto, Hirotsugu Roman, Richard J Nithipatikom, Kasem Campbell, William B Harder, David R |
| description | In the brain, pressure-induced myogenic constriction of cerebral arteriolar muscle contributes to autoregulation of cerebral blood flow (CBF). This study examined the role of 20-HETE in autoregulation of CBF in anesthetized rats. The expression of P-450 4A protein and mRNA was localized in isolated cerebral arteriolar muscle of rat by immunocytochemistry and in situ hybridization. The results of reverse transcriptase–polymerase chain reaction studies revealed that rat cerebral microvessels express cytochrome P-450 4A1, 4A2, 4A3, and 4A8 isoforms, some of which catalyze the formation of 20-HETE from arachidonic acid. Cerebral arterial microsomes incubated with [C]arachidonic acid produced 20-HETE. An elevation in transmural pressure from 20 to 140 mm Hg increased 20-HETE concentration by 6-fold in cerebral arteries as measured by gas chromatography/mass spectrometry. In vivo, inhibition of vascular 20-HETE formation with N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS), or its vasoconstrictor actions using 15-HETE or 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE), attenuated autoregulation of CBF to elevations of arterial pressure. In vitro application of DDMS, 15-HETE, or 20-HEDE eliminated pressure-induced constriction of rat middle cerebral arteries, and 20-HEDE and 15-HETE blocked the vasoconstriction action of 20-HETE. Taken together, these data suggest an important role for 20-HETE in the autoregulation of CBF. (Circ Res. 2000;87:60-65.) |
| doi_str_mv | 10.1161/01.res.87.1.60 |
| format | Article |
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This study examined the role of 20-HETE in autoregulation of CBF in anesthetized rats. The expression of P-450 4A protein and mRNA was localized in isolated cerebral arteriolar muscle of rat by immunocytochemistry and in situ hybridization. The results of reverse transcriptase–polymerase chain reaction studies revealed that rat cerebral microvessels express cytochrome P-450 4A1, 4A2, 4A3, and 4A8 isoforms, some of which catalyze the formation of 20-HETE from arachidonic acid. Cerebral arterial microsomes incubated with [C]arachidonic acid produced 20-HETE. An elevation in transmural pressure from 20 to 140 mm Hg increased 20-HETE concentration by 6-fold in cerebral arteries as measured by gas chromatography/mass spectrometry. In vivo, inhibition of vascular 20-HETE formation with N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS), or its vasoconstrictor actions using 15-HETE or 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE), attenuated autoregulation of CBF to elevations of arterial pressure. In vitro application of DDMS, 15-HETE, or 20-HEDE eliminated pressure-induced constriction of rat middle cerebral arteries, and 20-HEDE and 15-HETE blocked the vasoconstriction action of 20-HETE. Taken together, these data suggest an important role for 20-HETE in the autoregulation of CBF. (Circ Res. 2000;87:60-65.)</description><identifier>ISSN: 0009-7330</identifier><identifier>EISSN: 1524-4571</identifier><identifier>DOI: 10.1161/01.res.87.1.60</identifier><identifier>PMID: 10884373</identifier><identifier>CODEN: CIRUAL</identifier><language>eng</language><publisher>Hagerstown, MD: American Heart Association, Inc</publisher><subject>Amides - pharmacology ; Animals ; Biological and medical sciences ; Cerebral Arteries - physiology ; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges ; Cerebrovascular Circulation ; Cytochrome P-450 CYP4A ; Cytochrome P-450 Enzyme System - genetics ; Fundamental and applied biological sciences. Psychology ; Homeostasis ; Hydroxyeicosatetraenoic Acids - antagonists & inhibitors ; Hydroxyeicosatetraenoic Acids - physiology ; In Vitro Techniques ; Microsomes - metabolism ; Mixed Function Oxygenases - genetics ; Muscle, Smooth, Vascular - metabolism ; Rats ; RNA, Messenger - analysis ; Sulfones - pharmacology ; Vasoconstriction ; Vertebrates: nervous system and sense organs</subject><ispartof>Circulation research, 2000-07, Vol.87 (1), p.60-65</ispartof><rights>2000 American Heart Association, Inc.</rights><rights>2000 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Jul 7, 2000</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5782-937558a8498909638aa0157fc0bb84a22a81ab77fe6c3fd1c07f653da7d623373</citedby><cites>FETCH-LOGICAL-c5782-937558a8498909638aa0157fc0bb84a22a81ab77fe6c3fd1c07f653da7d623373</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3673,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1440578$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10884373$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gebremedhin, Debebe</creatorcontrib><creatorcontrib>Lange, Andrew R</creatorcontrib><creatorcontrib>Lowry, Timothy F</creatorcontrib><creatorcontrib>Taheri, M Reza</creatorcontrib><creatorcontrib>Birks, Eric K</creatorcontrib><creatorcontrib>Hudetz, Antal G</creatorcontrib><creatorcontrib>Narayanan, Jayashree</creatorcontrib><creatorcontrib>Falck, John R</creatorcontrib><creatorcontrib>Okamoto, Hirotsugu</creatorcontrib><creatorcontrib>Roman, Richard J</creatorcontrib><creatorcontrib>Nithipatikom, Kasem</creatorcontrib><creatorcontrib>Campbell, William B</creatorcontrib><creatorcontrib>Harder, David R</creatorcontrib><title>Production of 20-HETE and Its Role in Autoregulation of Cerebral Blood Flow</title><title>Circulation research</title><addtitle>Circ Res</addtitle><description>In the brain, pressure-induced myogenic constriction of cerebral arteriolar muscle contributes to autoregulation of cerebral blood flow (CBF). This study examined the role of 20-HETE in autoregulation of CBF in anesthetized rats. The expression of P-450 4A protein and mRNA was localized in isolated cerebral arteriolar muscle of rat by immunocytochemistry and in situ hybridization. The results of reverse transcriptase–polymerase chain reaction studies revealed that rat cerebral microvessels express cytochrome P-450 4A1, 4A2, 4A3, and 4A8 isoforms, some of which catalyze the formation of 20-HETE from arachidonic acid. Cerebral arterial microsomes incubated with [C]arachidonic acid produced 20-HETE. An elevation in transmural pressure from 20 to 140 mm Hg increased 20-HETE concentration by 6-fold in cerebral arteries as measured by gas chromatography/mass spectrometry. In vivo, inhibition of vascular 20-HETE formation with N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS), or its vasoconstrictor actions using 15-HETE or 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE), attenuated autoregulation of CBF to elevations of arterial pressure. In vitro application of DDMS, 15-HETE, or 20-HEDE eliminated pressure-induced constriction of rat middle cerebral arteries, and 20-HEDE and 15-HETE blocked the vasoconstriction action of 20-HETE. Taken together, these data suggest an important role for 20-HETE in the autoregulation of CBF. (Circ Res. 2000;87:60-65.)</description><subject>Amides - pharmacology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cerebral Arteries - physiology</subject><subject>Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges</subject><subject>Cerebrovascular Circulation</subject><subject>Cytochrome P-450 CYP4A</subject><subject>Cytochrome P-450 Enzyme System - genetics</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Homeostasis</subject><subject>Hydroxyeicosatetraenoic Acids - antagonists & inhibitors</subject><subject>Hydroxyeicosatetraenoic Acids - physiology</subject><subject>In Vitro Techniques</subject><subject>Microsomes - metabolism</subject><subject>Mixed Function Oxygenases - genetics</subject><subject>Muscle, Smooth, Vascular - metabolism</subject><subject>Rats</subject><subject>RNA, Messenger - analysis</subject><subject>Sulfones - pharmacology</subject><subject>Vasoconstriction</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0009-7330</issn><issn>1524-4571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpd0U1r3DAQBmARWprNttcciyglN7szkmzJx3TZfNBAS5qehSzLiVOtlUg2S_99FHZDQtFhdHhmGN4h5BihRKzxG2AZXSqVLLGs4YAssGKiEJXEd2QBAE0hOYdDcpTSPQAKzpoP5BBBKcElX5Afv2LoZjsNYaShpwyKi_XNmpqxo5dTotfBOzqM9HSeQnS3szcvcuWia6Px9LsPoaNnPmw_kve98cl92tcl-XO2vlldFFc_zy9Xp1eFraRiRcNlVSmjRKMaaGqujAGsZG-hbZUwjBmFppWyd7XlfYcWZF9XvDOyqxnPWy_JyW7uQwyPs0uT3gzJOu_N6MKctERWqyq3LMmX_-B9mOOYd9MMmUCVs8qo3CEbQ0rR9fohDhsT_2kE_ZyxBtTX699aSY26htzweT91bjeue8N3oWbwdQ9Mssb30Yx2SK9OCMhBZCZ2bBv85GL66-eti_rOGT_d6Xw74ICsYM8_mV-RKzL-BOt3kBM</recordid><startdate>20000707</startdate><enddate>20000707</enddate><creator>Gebremedhin, Debebe</creator><creator>Lange, Andrew R</creator><creator>Lowry, Timothy F</creator><creator>Taheri, M Reza</creator><creator>Birks, Eric K</creator><creator>Hudetz, Antal G</creator><creator>Narayanan, Jayashree</creator><creator>Falck, John R</creator><creator>Okamoto, Hirotsugu</creator><creator>Roman, Richard J</creator><creator>Nithipatikom, Kasem</creator><creator>Campbell, William B</creator><creator>Harder, David R</creator><general>American Heart Association, Inc</general><general>Lippincott</general><general>Lippincott Williams & Wilkins Ovid Technologies</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>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20000707</creationdate><title>Production of 20-HETE and Its Role in Autoregulation of Cerebral Blood Flow</title><author>Gebremedhin, Debebe ; Lange, Andrew R ; Lowry, Timothy F ; Taheri, M Reza ; Birks, Eric K ; Hudetz, Antal G ; Narayanan, Jayashree ; Falck, John R ; Okamoto, Hirotsugu ; Roman, Richard J ; Nithipatikom, Kasem ; Campbell, William B ; Harder, David R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5782-937558a8498909638aa0157fc0bb84a22a81ab77fe6c3fd1c07f653da7d623373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Amides - pharmacology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cerebral Arteries - physiology</topic><topic>Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges</topic><topic>Cerebrovascular Circulation</topic><topic>Cytochrome P-450 CYP4A</topic><topic>Cytochrome P-450 Enzyme System - genetics</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Homeostasis</topic><topic>Hydroxyeicosatetraenoic Acids - antagonists & inhibitors</topic><topic>Hydroxyeicosatetraenoic Acids - physiology</topic><topic>In Vitro Techniques</topic><topic>Microsomes - metabolism</topic><topic>Mixed Function Oxygenases - genetics</topic><topic>Muscle, Smooth, Vascular - metabolism</topic><topic>Rats</topic><topic>RNA, Messenger - analysis</topic><topic>Sulfones - pharmacology</topic><topic>Vasoconstriction</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gebremedhin, Debebe</creatorcontrib><creatorcontrib>Lange, Andrew R</creatorcontrib><creatorcontrib>Lowry, Timothy F</creatorcontrib><creatorcontrib>Taheri, M Reza</creatorcontrib><creatorcontrib>Birks, Eric K</creatorcontrib><creatorcontrib>Hudetz, Antal G</creatorcontrib><creatorcontrib>Narayanan, Jayashree</creatorcontrib><creatorcontrib>Falck, John R</creatorcontrib><creatorcontrib>Okamoto, Hirotsugu</creatorcontrib><creatorcontrib>Roman, Richard J</creatorcontrib><creatorcontrib>Nithipatikom, Kasem</creatorcontrib><creatorcontrib>Campbell, William B</creatorcontrib><creatorcontrib>Harder, David R</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>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gebremedhin, Debebe</au><au>Lange, Andrew R</au><au>Lowry, Timothy F</au><au>Taheri, M Reza</au><au>Birks, Eric K</au><au>Hudetz, Antal G</au><au>Narayanan, Jayashree</au><au>Falck, John R</au><au>Okamoto, Hirotsugu</au><au>Roman, Richard J</au><au>Nithipatikom, Kasem</au><au>Campbell, William B</au><au>Harder, David R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Production of 20-HETE and Its Role in Autoregulation of Cerebral Blood Flow</atitle><jtitle>Circulation research</jtitle><addtitle>Circ Res</addtitle><date>2000-07-07</date><risdate>2000</risdate><volume>87</volume><issue>1</issue><spage>60</spage><epage>65</epage><pages>60-65</pages><issn>0009-7330</issn><eissn>1524-4571</eissn><coden>CIRUAL</coden><abstract>In the brain, pressure-induced myogenic constriction of cerebral arteriolar muscle contributes to autoregulation of cerebral blood flow (CBF). This study examined the role of 20-HETE in autoregulation of CBF in anesthetized rats. The expression of P-450 4A protein and mRNA was localized in isolated cerebral arteriolar muscle of rat by immunocytochemistry and in situ hybridization. The results of reverse transcriptase–polymerase chain reaction studies revealed that rat cerebral microvessels express cytochrome P-450 4A1, 4A2, 4A3, and 4A8 isoforms, some of which catalyze the formation of 20-HETE from arachidonic acid. Cerebral arterial microsomes incubated with [C]arachidonic acid produced 20-HETE. An elevation in transmural pressure from 20 to 140 mm Hg increased 20-HETE concentration by 6-fold in cerebral arteries as measured by gas chromatography/mass spectrometry. In vivo, inhibition of vascular 20-HETE formation with N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS), or its vasoconstrictor actions using 15-HETE or 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE), attenuated autoregulation of CBF to elevations of arterial pressure. In vitro application of DDMS, 15-HETE, or 20-HEDE eliminated pressure-induced constriction of rat middle cerebral arteries, and 20-HEDE and 15-HETE blocked the vasoconstriction action of 20-HETE. Taken together, these data suggest an important role for 20-HETE in the autoregulation of CBF. (Circ Res. 2000;87:60-65.)</abstract><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>10884373</pmid><doi>10.1161/01.res.87.1.60</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amides - pharmacology Animals Biological and medical sciences Cerebral Arteries - physiology Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges Cerebrovascular Circulation Cytochrome P-450 CYP4A Cytochrome P-450 Enzyme System - genetics Fundamental and applied biological sciences. Psychology Homeostasis Hydroxyeicosatetraenoic Acids - antagonists & inhibitors Hydroxyeicosatetraenoic Acids - physiology In Vitro Techniques Microsomes - metabolism Mixed Function Oxygenases - genetics Muscle, Smooth, Vascular - metabolism Rats RNA, Messenger - analysis Sulfones - pharmacology Vasoconstriction Vertebrates: nervous system and sense organs |
| title | Production of 20-HETE and Its Role in Autoregulation of Cerebral Blood Flow |
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