Adrenic Acid Metabolites as Endogenous Endothelium-Derived and Zona Glomerulosa-Derived Hyperpolarizing Factors
Adrenic acid (docosatetraenoic acid), an abundant fatty acid in the adrenal gland, is identical to arachidonic acid except for 2 additional carbons on the carboxyl end. Adrenic acid is metabolized by cyclooxygenases, cytochrome P450s, and lipoxygenases; however, little is known regarding the role of...
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| Veröffentlicht in: | Hypertension (Dallas, Tex. 1979) Tex. 1979), 2010-02, Vol.55 (2, Part 2 Suppl), p.547-554 |
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| creator | Kopf, Phillip G Zhang, David X Gauthier, Kathryn M Nithipatikom, Kasem Yi, Xiu-Yu Falck, John R Campbell, William B |
| description | Adrenic acid (docosatetraenoic acid), an abundant fatty acid in the adrenal gland, is identical to arachidonic acid except for 2 additional carbons on the carboxyl end. Adrenic acid is metabolized by cyclooxygenases, cytochrome P450s, and lipoxygenases; however, little is known regarding the role of adrenic acid and its metabolites in vascular tone. Because of its abundance in the adrenal gland, we investigated the role of adrenic acid in vascular tone of bovine adrenal cortical arteries and its metabolism by bovine adrenal zona glomerulosa cells. In adrenal cortical arteries, adrenic acid caused concentration-dependent relaxations, which were inhibited by the epoxyeicosatrienoic acid antagonist 14,15-epoxyeicosa-5(Z)-enoic acid and the cytochrome P450 inhibitor SKF-525A. The large-conductance calcium-activated potassium channel blocker iberiotoxin or removal of the endothelium abolished these relaxations. Reverse-phase high-pressure liquid chromatography and liquid chromatography/mass spectrometry isolated and identified numerous adrenic acid metabolites from zona glomerulosa cells, including dihomo-epoxyeicosatrienoic acids and dihomo-prostaglandins. In denuded adrenal cortical arteries, adrenic acid caused concentration-dependent relaxations in the presence of zona glomerulosa cells but not in their absence. These relaxations were inhibited by SKF-525A, 14,15-epoxyeicosa-5(Z)-enoic acid, and iberiotoxin. Dihomo-16,17-epoxyeicosatrienoic acid caused concentration-dependent relaxations of adrenal cortical arteries, which were inhibited by 14,15-epoxyeicosa-5(Z)-enoic acid and high potassium. Our results suggest that adrenic acid relaxations of bovine adrenal cortical arteries are mediated by endothelial and zona glomerulosa cell cytochrome P450 metabolites. Thus, adrenic acid metabolites could function as endogenous endothelium-derived and zona glomerulosa-derived hyperpolarizing factors in the adrenal cortex and contribute to the regulation of adrenal blood flow. |
| doi_str_mv | 10.1161/HYPERTENSIONAHA.109.144147 |
| format | Article |
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Adrenic acid is metabolized by cyclooxygenases, cytochrome P450s, and lipoxygenases; however, little is known regarding the role of adrenic acid and its metabolites in vascular tone. Because of its abundance in the adrenal gland, we investigated the role of adrenic acid in vascular tone of bovine adrenal cortical arteries and its metabolism by bovine adrenal zona glomerulosa cells. In adrenal cortical arteries, adrenic acid caused concentration-dependent relaxations, which were inhibited by the epoxyeicosatrienoic acid antagonist 14,15-epoxyeicosa-5(Z)-enoic acid and the cytochrome P450 inhibitor SKF-525A. The large-conductance calcium-activated potassium channel blocker iberiotoxin or removal of the endothelium abolished these relaxations. Reverse-phase high-pressure liquid chromatography and liquid chromatography/mass spectrometry isolated and identified numerous adrenic acid metabolites from zona glomerulosa cells, including dihomo-epoxyeicosatrienoic acids and dihomo-prostaglandins. In denuded adrenal cortical arteries, adrenic acid caused concentration-dependent relaxations in the presence of zona glomerulosa cells but not in their absence. These relaxations were inhibited by SKF-525A, 14,15-epoxyeicosa-5(Z)-enoic acid, and iberiotoxin. Dihomo-16,17-epoxyeicosatrienoic acid caused concentration-dependent relaxations of adrenal cortical arteries, which were inhibited by 14,15-epoxyeicosa-5(Z)-enoic acid and high potassium. Our results suggest that adrenic acid relaxations of bovine adrenal cortical arteries are mediated by endothelial and zona glomerulosa cell cytochrome P450 metabolites. Thus, adrenic acid metabolites could function as endogenous endothelium-derived and zona glomerulosa-derived hyperpolarizing factors in the adrenal cortex and contribute to the regulation of adrenal blood flow.</description><identifier>ISSN: 0194-911X</identifier><identifier>EISSN: 1524-4563</identifier><identifier>DOI: 10.1161/HYPERTENSIONAHA.109.144147</identifier><identifier>PMID: 20038752</identifier><identifier>CODEN: HPRTDN</identifier><language>eng</language><publisher>Hagerstown, MD: American Heart Association, Inc</publisher><subject>Adrenal Glands - blood supply ; Adrenal Glands - metabolism ; Analysis of Variance ; Animals ; Arterial hypertension. Arterial hypotension ; Biological and medical sciences ; Biological Factors - metabolism ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cardiovascular system ; Cattle ; Cells, Cultured ; Chromatography, High Pressure Liquid ; Cytochrome P-450 Enzyme System - metabolism ; Endothelium, Vascular - metabolism ; Erucic Acids - metabolism ; Erucic Acids - pharmacology ; Fatty Acids, Unsaturated ; Medical sciences ; Pharmacology. Drug treatments ; Potassium Channels, Calcium-Activated - pharmacology ; Proadifen - pharmacology ; Probability ; Vascular Resistance - drug effects ; Vascular Resistance - physiology ; Vasodilation - drug effects ; Vasodilation - physiology ; Vasodilator agents. Cerebral vasodilators ; Zona Glomerulosa - blood supply ; Zona Glomerulosa - metabolism</subject><ispartof>Hypertension (Dallas, Tex. 1979), 2010-02, Vol.55 (2, Part 2 Suppl), p.547-554</ispartof><rights>2010 American Heart Association, Inc.</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4938-995efc1642a7cbfe8a44643d4ea5481c4cc946fd429772aa00342b86624defdc3</citedby><cites>FETCH-LOGICAL-c4938-995efc1642a7cbfe8a44643d4ea5481c4cc946fd429772aa00342b86624defdc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>310,311,315,781,785,790,791,3688,23935,23936,25145,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22446299$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20038752$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kopf, Phillip G</creatorcontrib><creatorcontrib>Zhang, David X</creatorcontrib><creatorcontrib>Gauthier, Kathryn M</creatorcontrib><creatorcontrib>Nithipatikom, Kasem</creatorcontrib><creatorcontrib>Yi, Xiu-Yu</creatorcontrib><creatorcontrib>Falck, John R</creatorcontrib><creatorcontrib>Campbell, William B</creatorcontrib><title>Adrenic Acid Metabolites as Endogenous Endothelium-Derived and Zona Glomerulosa-Derived Hyperpolarizing Factors</title><title>Hypertension (Dallas, Tex. 1979)</title><addtitle>Hypertension</addtitle><description>Adrenic acid (docosatetraenoic acid), an abundant fatty acid in the adrenal gland, is identical to arachidonic acid except for 2 additional carbons on the carboxyl end. Adrenic acid is metabolized by cyclooxygenases, cytochrome P450s, and lipoxygenases; however, little is known regarding the role of adrenic acid and its metabolites in vascular tone. Because of its abundance in the adrenal gland, we investigated the role of adrenic acid in vascular tone of bovine adrenal cortical arteries and its metabolism by bovine adrenal zona glomerulosa cells. In adrenal cortical arteries, adrenic acid caused concentration-dependent relaxations, which were inhibited by the epoxyeicosatrienoic acid antagonist 14,15-epoxyeicosa-5(Z)-enoic acid and the cytochrome P450 inhibitor SKF-525A. The large-conductance calcium-activated potassium channel blocker iberiotoxin or removal of the endothelium abolished these relaxations. Reverse-phase high-pressure liquid chromatography and liquid chromatography/mass spectrometry isolated and identified numerous adrenic acid metabolites from zona glomerulosa cells, including dihomo-epoxyeicosatrienoic acids and dihomo-prostaglandins. In denuded adrenal cortical arteries, adrenic acid caused concentration-dependent relaxations in the presence of zona glomerulosa cells but not in their absence. These relaxations were inhibited by SKF-525A, 14,15-epoxyeicosa-5(Z)-enoic acid, and iberiotoxin. Dihomo-16,17-epoxyeicosatrienoic acid caused concentration-dependent relaxations of adrenal cortical arteries, which were inhibited by 14,15-epoxyeicosa-5(Z)-enoic acid and high potassium. Our results suggest that adrenic acid relaxations of bovine adrenal cortical arteries are mediated by endothelial and zona glomerulosa cell cytochrome P450 metabolites. Thus, adrenic acid metabolites could function as endogenous endothelium-derived and zona glomerulosa-derived hyperpolarizing factors in the adrenal cortex and contribute to the regulation of adrenal blood flow.</description><subject>Adrenal Glands - blood supply</subject><subject>Adrenal Glands - metabolism</subject><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Arterial hypertension. Arterial hypotension</subject><subject>Biological and medical sciences</subject><subject>Biological Factors - metabolism</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular system</subject><subject>Cattle</subject><subject>Cells, Cultured</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Erucic Acids - metabolism</subject><subject>Erucic Acids - pharmacology</subject><subject>Fatty Acids, Unsaturated</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Potassium Channels, Calcium-Activated - pharmacology</subject><subject>Proadifen - pharmacology</subject><subject>Probability</subject><subject>Vascular Resistance - drug effects</subject><subject>Vascular Resistance - physiology</subject><subject>Vasodilation - drug effects</subject><subject>Vasodilation - physiology</subject><subject>Vasodilator agents. Cerebral vasodilators</subject><subject>Zona Glomerulosa - blood supply</subject><subject>Zona Glomerulosa - metabolism</subject><issn>0194-911X</issn><issn>1524-4563</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkNtuFDEMhiNERbeFV0AjJC5nSTKeQ7gblW23Ug8IigTcjLyJpxvITlbJDFV5-gZNKRK-sWV_v2X_jL0RfClEJd6tv31cfbpZXX0-v75q1-1ScLUUAALqZ2whSgk5lFXxnC24UJArIb4esqMYf3CeKKhfsEPJedHUpVww35pAg9VZq63JLmnEjXd2pJhhzFaD8bc0-Gkuxy05O-3yDxTsLzIZDib77gfMzpzfUZicj_g0XN_vKey9w2B_2-E2O0U9-hBfsoMeXaRXj_mYfTld3Zys84vrs_OT9iLXoIomV6qkXosKJNZ601ODABUUBghLaIQGrRVUvQGp6loipn9AbpqqkmCoN7o4Zu_nvTr4GAP13T7YHYb7TvDuj4vdfy6mvupmF5P49SzeT5sdmSfpX9sS8PYRwKjR9QEHbeM_TqZrpVKJg5m7826kEH-66Y5CtyV047bjKUBWTS654DwtF3nqiKZ4ALR3jnQ</recordid><startdate>201002</startdate><enddate>201002</enddate><creator>Kopf, Phillip G</creator><creator>Zhang, David X</creator><creator>Gauthier, Kathryn M</creator><creator>Nithipatikom, Kasem</creator><creator>Yi, Xiu-Yu</creator><creator>Falck, John R</creator><creator>Campbell, William B</creator><general>American Heart Association, Inc</general><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></search><sort><creationdate>201002</creationdate><title>Adrenic Acid Metabolites as Endogenous Endothelium-Derived and Zona Glomerulosa-Derived Hyperpolarizing Factors</title><author>Kopf, Phillip G ; Zhang, David X ; Gauthier, Kathryn M ; Nithipatikom, Kasem ; Yi, Xiu-Yu ; Falck, John R ; Campbell, William B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4938-995efc1642a7cbfe8a44643d4ea5481c4cc946fd429772aa00342b86624defdc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adrenal Glands - blood supply</topic><topic>Adrenal Glands - metabolism</topic><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Arterial hypertension. Arterial hypotension</topic><topic>Biological and medical sciences</topic><topic>Biological Factors - metabolism</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Cardiovascular system</topic><topic>Cattle</topic><topic>Cells, Cultured</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Erucic Acids - metabolism</topic><topic>Erucic Acids - pharmacology</topic><topic>Fatty Acids, Unsaturated</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Potassium Channels, Calcium-Activated - pharmacology</topic><topic>Proadifen - pharmacology</topic><topic>Probability</topic><topic>Vascular Resistance - drug effects</topic><topic>Vascular Resistance - physiology</topic><topic>Vasodilation - drug effects</topic><topic>Vasodilation - physiology</topic><topic>Vasodilator agents. Cerebral vasodilators</topic><topic>Zona Glomerulosa - blood supply</topic><topic>Zona Glomerulosa - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kopf, Phillip G</creatorcontrib><creatorcontrib>Zhang, David X</creatorcontrib><creatorcontrib>Gauthier, Kathryn M</creatorcontrib><creatorcontrib>Nithipatikom, Kasem</creatorcontrib><creatorcontrib>Yi, Xiu-Yu</creatorcontrib><creatorcontrib>Falck, John R</creatorcontrib><creatorcontrib>Campbell, William B</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><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kopf, Phillip G</au><au>Zhang, David X</au><au>Gauthier, Kathryn M</au><au>Nithipatikom, Kasem</au><au>Yi, Xiu-Yu</au><au>Falck, John R</au><au>Campbell, William B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adrenic Acid Metabolites as Endogenous Endothelium-Derived and Zona Glomerulosa-Derived Hyperpolarizing Factors</atitle><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle><addtitle>Hypertension</addtitle><date>2010-02</date><risdate>2010</risdate><volume>55</volume><issue>2, Part 2 Suppl</issue><spage>547</spage><epage>554</epage><pages>547-554</pages><issn>0194-911X</issn><eissn>1524-4563</eissn><coden>HPRTDN</coden><abstract>Adrenic acid (docosatetraenoic acid), an abundant fatty acid in the adrenal gland, is identical to arachidonic acid except for 2 additional carbons on the carboxyl end. Adrenic acid is metabolized by cyclooxygenases, cytochrome P450s, and lipoxygenases; however, little is known regarding the role of adrenic acid and its metabolites in vascular tone. Because of its abundance in the adrenal gland, we investigated the role of adrenic acid in vascular tone of bovine adrenal cortical arteries and its metabolism by bovine adrenal zona glomerulosa cells. In adrenal cortical arteries, adrenic acid caused concentration-dependent relaxations, which were inhibited by the epoxyeicosatrienoic acid antagonist 14,15-epoxyeicosa-5(Z)-enoic acid and the cytochrome P450 inhibitor SKF-525A. The large-conductance calcium-activated potassium channel blocker iberiotoxin or removal of the endothelium abolished these relaxations. Reverse-phase high-pressure liquid chromatography and liquid chromatography/mass spectrometry isolated and identified numerous adrenic acid metabolites from zona glomerulosa cells, including dihomo-epoxyeicosatrienoic acids and dihomo-prostaglandins. In denuded adrenal cortical arteries, adrenic acid caused concentration-dependent relaxations in the presence of zona glomerulosa cells but not in their absence. These relaxations were inhibited by SKF-525A, 14,15-epoxyeicosa-5(Z)-enoic acid, and iberiotoxin. Dihomo-16,17-epoxyeicosatrienoic acid caused concentration-dependent relaxations of adrenal cortical arteries, which were inhibited by 14,15-epoxyeicosa-5(Z)-enoic acid and high potassium. Our results suggest that adrenic acid relaxations of bovine adrenal cortical arteries are mediated by endothelial and zona glomerulosa cell cytochrome P450 metabolites. Thus, adrenic acid metabolites could function as endogenous endothelium-derived and zona glomerulosa-derived hyperpolarizing factors in the adrenal cortex and contribute to the regulation of adrenal blood flow.</abstract><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>20038752</pmid><doi>10.1161/HYPERTENSIONAHA.109.144147</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0194-911X |
| ispartof | Hypertension (Dallas, Tex. 1979), 2010-02, Vol.55 (2, Part 2 Suppl), p.547-554 |
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| source | MEDLINE; American Heart Association Journals; Journals@Ovid Complete; EZB-FREE-00999 freely available EZB journals |
| subjects | Adrenal Glands - blood supply Adrenal Glands - metabolism Analysis of Variance Animals Arterial hypertension. Arterial hypotension Biological and medical sciences Biological Factors - metabolism Blood and lymphatic vessels Cardiology. Vascular system Cardiovascular system Cattle Cells, Cultured Chromatography, High Pressure Liquid Cytochrome P-450 Enzyme System - metabolism Endothelium, Vascular - metabolism Erucic Acids - metabolism Erucic Acids - pharmacology Fatty Acids, Unsaturated Medical sciences Pharmacology. Drug treatments Potassium Channels, Calcium-Activated - pharmacology Proadifen - pharmacology Probability Vascular Resistance - drug effects Vascular Resistance - physiology Vasodilation - drug effects Vasodilation - physiology Vasodilator agents. Cerebral vasodilators Zona Glomerulosa - blood supply Zona Glomerulosa - metabolism |
| title | Adrenic Acid Metabolites as Endogenous Endothelium-Derived and Zona Glomerulosa-Derived Hyperpolarizing Factors |
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