Human pulmonary arteries dilate to 20-HETE, an endogenous eicosanoid of lung tissue
E. K. Birks, M. Bousamra, K. Presberg, J. A. Marsh, R. M. Effros and E. R. Jacobs Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA. We investigated the effect of 20-hydroxyeicosatetraenoic acid (20-HETE), an arachidonic acid metabolite of the cytochrome P-450 (cP450) 4A p...
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| Veröffentlicht in: | American journal of physiology. Lung cellular and molecular physiology 1997-05, Vol.272 (5), p.823-L829 |
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| container_title | American journal of physiology. Lung cellular and molecular physiology |
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| creator | Birks, E. K Bousamra, M Presberg, K Marsh, J. A Effros, R. M Jacobs, E. R |
| description | E. K. Birks, M. Bousamra, K. Presberg, J. A. Marsh, R. M. Effros and E. R. Jacobs
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA.
We investigated the effect of 20-hydroxyeicosatetraenoic acid (20-HETE), an
arachidonic acid metabolite of the cytochrome P-450 (cP450) 4A pathway, on
human pulmonary arterial tone. 20-HETE elicited a dose-dependent and
indomethacin-inhibitable vasodilation of isolated small pulmonary arteries.
Whole lung microsomes metabolized [24C]arachidonic acid into 20-HETE and a
variety of leukotrienes, epoxyeicosatrienoic acids, and prostanoids.
Indomethacin blocked formation of prostanoids without effects on the
conversion of arachidonate into 20-HETE, 20-HETE was converted by lung
microsomes into prostanoids, raising the possibility that 20-HETE may be
metabolized by cyclooxygenase enzymes in vascular tissue to a vasodilatory
compound. Western blots probed with a polyclonal antibody to cP450 4A
identified a protein of approximately 50 kDa immunologically similar to the
cP450 4A in rat liver. We conclude that small arteries from human lungs
dilate upon exposure to 20-HETE in a cyclooxygenase-dependent manner and
that the proteins and enzymatic activity required to synthesize this
product are present in lungs. Our observations suggest that cP450 enzyme
products could be endogenous modulators of pulmonary vascular tone. |
| doi_str_mv | 10.1152/ajplung.1997.272.5.L823 |
| format | Article |
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Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA.
We investigated the effect of 20-hydroxyeicosatetraenoic acid (20-HETE), an
arachidonic acid metabolite of the cytochrome P-450 (cP450) 4A pathway, on
human pulmonary arterial tone. 20-HETE elicited a dose-dependent and
indomethacin-inhibitable vasodilation of isolated small pulmonary arteries.
Whole lung microsomes metabolized [24C]arachidonic acid into 20-HETE and a
variety of leukotrienes, epoxyeicosatrienoic acids, and prostanoids.
Indomethacin blocked formation of prostanoids without effects on the
conversion of arachidonate into 20-HETE, 20-HETE was converted by lung
microsomes into prostanoids, raising the possibility that 20-HETE may be
metabolized by cyclooxygenase enzymes in vascular tissue to a vasodilatory
compound. Western blots probed with a polyclonal antibody to cP450 4A
identified a protein of approximately 50 kDa immunologically similar to the
cP450 4A in rat liver. We conclude that small arteries from human lungs
dilate upon exposure to 20-HETE in a cyclooxygenase-dependent manner and
that the proteins and enzymatic activity required to synthesize this
product are present in lungs. Our observations suggest that cP450 enzyme
products could be endogenous modulators of pulmonary vascular tone.</description><identifier>ISSN: 1040-0605</identifier><identifier>ISSN: 0002-9513</identifier><identifier>EISSN: 1522-1504</identifier><identifier>EISSN: 2163-5773</identifier><identifier>DOI: 10.1152/ajplung.1997.272.5.L823</identifier><identifier>PMID: 9176244</identifier><identifier>CODEN: AJPHAP</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>Animals ; Arachidonic Acid - metabolism ; Cats ; Cattle ; Dose-Response Relationship, Drug ; Eicosanoids - metabolism ; Female ; Ferrets ; Humans ; Hydroxyeicosatetraenoic Acids - pharmacology ; In Vitro Techniques ; Lung - metabolism ; Male ; Middle Aged ; Pulmonary Artery - drug effects ; Rabbits ; Rats ; Vasodilation</subject><ispartof>American journal of physiology. Lung cellular and molecular physiology, 1997-05, Vol.272 (5), p.823-L829</ispartof><rights>Copyright American Physiological Society May 1997</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c373t-2cbb64b5e6796fe03f32df32843a36b7116533bacf19515f781ab140379760b33</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,3026,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9176244$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Birks, E. K</creatorcontrib><creatorcontrib>Bousamra, M</creatorcontrib><creatorcontrib>Presberg, K</creatorcontrib><creatorcontrib>Marsh, J. A</creatorcontrib><creatorcontrib>Effros, R. M</creatorcontrib><creatorcontrib>Jacobs, E. R</creatorcontrib><title>Human pulmonary arteries dilate to 20-HETE, an endogenous eicosanoid of lung tissue</title><title>American journal of physiology. Lung cellular and molecular physiology</title><addtitle>Am J Physiol</addtitle><description>E. K. Birks, M. Bousamra, K. Presberg, J. A. Marsh, R. M. Effros and E. R. Jacobs
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA.
We investigated the effect of 20-hydroxyeicosatetraenoic acid (20-HETE), an
arachidonic acid metabolite of the cytochrome P-450 (cP450) 4A pathway, on
human pulmonary arterial tone. 20-HETE elicited a dose-dependent and
indomethacin-inhibitable vasodilation of isolated small pulmonary arteries.
Whole lung microsomes metabolized [24C]arachidonic acid into 20-HETE and a
variety of leukotrienes, epoxyeicosatrienoic acids, and prostanoids.
Indomethacin blocked formation of prostanoids without effects on the
conversion of arachidonate into 20-HETE, 20-HETE was converted by lung
microsomes into prostanoids, raising the possibility that 20-HETE may be
metabolized by cyclooxygenase enzymes in vascular tissue to a vasodilatory
compound. Western blots probed with a polyclonal antibody to cP450 4A
identified a protein of approximately 50 kDa immunologically similar to the
cP450 4A in rat liver. We conclude that small arteries from human lungs
dilate upon exposure to 20-HETE in a cyclooxygenase-dependent manner and
that the proteins and enzymatic activity required to synthesize this
product are present in lungs. Our observations suggest that cP450 enzyme
products could be endogenous modulators of pulmonary vascular tone.</description><subject>Animals</subject><subject>Arachidonic Acid - metabolism</subject><subject>Cats</subject><subject>Cattle</subject><subject>Dose-Response Relationship, Drug</subject><subject>Eicosanoids - metabolism</subject><subject>Female</subject><subject>Ferrets</subject><subject>Humans</subject><subject>Hydroxyeicosatetraenoic Acids - pharmacology</subject><subject>In Vitro Techniques</subject><subject>Lung - metabolism</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Pulmonary Artery - drug effects</subject><subject>Rabbits</subject><subject>Rats</subject><subject>Vasodilation</subject><issn>1040-0605</issn><issn>0002-9513</issn><issn>1522-1504</issn><issn>2163-5773</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkE-L1EAQxRtR1t3VjyA2HjxtYlX_nRxlGR1hwIPruekknZkeknTsTljm29thhkU8FFXwXj0eP0I-IpSIkn2xp6lfxkOJVaVLplkpy_2G8VfkNqusQAnidb5BQAEK5Ftyl9IJACSAuiE3FWrFhLglv3bLYEc6Lf0QRhvP1MbZRe8SbX1vZ0fnQBkUu-3T9oFmoxvbcHBjWBJ1vgnJjsG3NHR0bUNnn9Li3pE3ne2Te3_d9-T3t-3T467Y__z-4_Hrvmi45nPBmrpWopZO6Up1DnjHWZtnI7jlqtaISnJe26bDSqLs9AZtjQK4rrSCmvN78vmSO8XwZ3FpNoNPjet7O7pc0OgKBCLDbPz0n_EUljjmboahElqgXE36YmpiSCm6zkzRDxmJQTArc3NlblbmJjM30qzM8-eHa_xSD659-btCznpx0Y_-cHz20ZnpeE4-9OFwfgn9J-8v8N2NzQ</recordid><startdate>19970501</startdate><enddate>19970501</enddate><creator>Birks, E. K</creator><creator>Bousamra, M</creator><creator>Presberg, K</creator><creator>Marsh, J. A</creator><creator>Effros, R. M</creator><creator>Jacobs, E. R</creator><general>American Physiological Society</general><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></search><sort><creationdate>19970501</creationdate><title>Human pulmonary arteries dilate to 20-HETE, an endogenous eicosanoid of lung tissue</title><author>Birks, E. K ; Bousamra, M ; Presberg, K ; Marsh, J. A ; Effros, R. M ; Jacobs, E. R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c373t-2cbb64b5e6796fe03f32df32843a36b7116533bacf19515f781ab140379760b33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Animals</topic><topic>Arachidonic Acid - metabolism</topic><topic>Cats</topic><topic>Cattle</topic><topic>Dose-Response Relationship, Drug</topic><topic>Eicosanoids - metabolism</topic><topic>Female</topic><topic>Ferrets</topic><topic>Humans</topic><topic>Hydroxyeicosatetraenoic Acids - pharmacology</topic><topic>In Vitro Techniques</topic><topic>Lung - metabolism</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Pulmonary Artery - drug effects</topic><topic>Rabbits</topic><topic>Rats</topic><topic>Vasodilation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Birks, E. K</creatorcontrib><creatorcontrib>Bousamra, M</creatorcontrib><creatorcontrib>Presberg, K</creatorcontrib><creatorcontrib>Marsh, J. A</creatorcontrib><creatorcontrib>Effros, R. M</creatorcontrib><creatorcontrib>Jacobs, E. R</creatorcontrib><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><jtitle>American journal of physiology. Lung cellular and molecular physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Birks, E. K</au><au>Bousamra, M</au><au>Presberg, K</au><au>Marsh, J. A</au><au>Effros, R. M</au><au>Jacobs, E. R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human pulmonary arteries dilate to 20-HETE, an endogenous eicosanoid of lung tissue</atitle><jtitle>American journal of physiology. Lung cellular and molecular physiology</jtitle><addtitle>Am J Physiol</addtitle><date>1997-05-01</date><risdate>1997</risdate><volume>272</volume><issue>5</issue><spage>823</spage><epage>L829</epage><pages>823-L829</pages><issn>1040-0605</issn><issn>0002-9513</issn><eissn>1522-1504</eissn><eissn>2163-5773</eissn><coden>AJPHAP</coden><abstract>E. K. Birks, M. Bousamra, K. Presberg, J. A. Marsh, R. M. Effros and E. R. Jacobs
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA.
We investigated the effect of 20-hydroxyeicosatetraenoic acid (20-HETE), an
arachidonic acid metabolite of the cytochrome P-450 (cP450) 4A pathway, on
human pulmonary arterial tone. 20-HETE elicited a dose-dependent and
indomethacin-inhibitable vasodilation of isolated small pulmonary arteries.
Whole lung microsomes metabolized [24C]arachidonic acid into 20-HETE and a
variety of leukotrienes, epoxyeicosatrienoic acids, and prostanoids.
Indomethacin blocked formation of prostanoids without effects on the
conversion of arachidonate into 20-HETE, 20-HETE was converted by lung
microsomes into prostanoids, raising the possibility that 20-HETE may be
metabolized by cyclooxygenase enzymes in vascular tissue to a vasodilatory
compound. Western blots probed with a polyclonal antibody to cP450 4A
identified a protein of approximately 50 kDa immunologically similar to the
cP450 4A in rat liver. We conclude that small arteries from human lungs
dilate upon exposure to 20-HETE in a cyclooxygenase-dependent manner and
that the proteins and enzymatic activity required to synthesize this
product are present in lungs. Our observations suggest that cP450 enzyme
products could be endogenous modulators of pulmonary vascular tone.</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>9176244</pmid><doi>10.1152/ajplung.1997.272.5.L823</doi></addata></record> |
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| ispartof | American journal of physiology. Lung cellular and molecular physiology, 1997-05, Vol.272 (5), p.823-L829 |
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| source | MEDLINE; American Physiological Society; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Arachidonic Acid - metabolism Cats Cattle Dose-Response Relationship, Drug Eicosanoids - metabolism Female Ferrets Humans Hydroxyeicosatetraenoic Acids - pharmacology In Vitro Techniques Lung - metabolism Male Middle Aged Pulmonary Artery - drug effects Rabbits Rats Vasodilation |
| title | Human pulmonary arteries dilate to 20-HETE, an endogenous eicosanoid of lung tissue |
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