Sphingosine Kinase–Dependent Activation of Endothelial Nitric Oxide Synthase by Angiotensin II
OBJECTIVE—In addition to their role in programmed cell death, cell survival, and cell growth, sphingolipid metabolites such as ceramide, sphingosine, and sphingosine-1-phosphate have vasoactive properties. Besides their occurrence in blood, they can also be formed locally in the vascular wall itself...
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Veröffentlicht in: | Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2006-09, Vol.26 (9), p.2043-2048 |
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creator | Mulders, Arthur C.M Hendriks-Balk, Mariëlle C Mathy, Marie-Jeanne Michel, Martin C Alewijnse, Astrid E Peters, Stephan L.M |
description | OBJECTIVE—In addition to their role in programmed cell death, cell survival, and cell growth, sphingolipid metabolites such as ceramide, sphingosine, and sphingosine-1-phosphate have vasoactive properties. Besides their occurrence in blood, they can also be formed locally in the vascular wall itself in response to external stimuli. This study was performed to investigate whether vasoactive compounds modulate sphingolipid metabolism in the vascular wall and how this might contribute to the vascular responses.
METHODS AND RESULTS—In isolated rat carotid arteries, the contractile responses to angiotensin II are enhanced by the sphingosine kinase inhibitor dimethylsphingosine. Endothelium removal or NO synthase inhibition by N-nitro-l-arginine results in a similar enhancement. Angiotensin II concentration-dependently induces NO production in an endothelial cell line, which can be diminished by dimethylsphingosine. Using immunoblotting and intracellular calcium measurements, we demonstrate that this sphingosine kinase–dependent endothelial NO synthase activation is mediated via both phosphatidylinositol 3-kinase/Akt and calcium-dependent pathways.
CONCLUSIONS—Angiotensin II induces a sphingosine kinase–dependent activation of endothelial NO synthase, which partially counteracts the contractile responses in isolated artery preparations. This pathway may be of importance under pathological circumstances with reduced NO bioavailability. Moreover, a disturbed sphingolipid metabolism in the vascular wall may lead to reduced NO bioavailability and endothelial dysfunction. |
doi_str_mv | 10.1161/01.ATV.0000237569.95046.b9 |
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METHODS AND RESULTS—In isolated rat carotid arteries, the contractile responses to angiotensin II are enhanced by the sphingosine kinase inhibitor dimethylsphingosine. Endothelium removal or NO synthase inhibition by N-nitro-l-arginine results in a similar enhancement. Angiotensin II concentration-dependently induces NO production in an endothelial cell line, which can be diminished by dimethylsphingosine. Using immunoblotting and intracellular calcium measurements, we demonstrate that this sphingosine kinase–dependent endothelial NO synthase activation is mediated via both phosphatidylinositol 3-kinase/Akt and calcium-dependent pathways.
CONCLUSIONS—Angiotensin II induces a sphingosine kinase–dependent activation of endothelial NO synthase, which partially counteracts the contractile responses in isolated artery preparations. This pathway may be of importance under pathological circumstances with reduced NO bioavailability. Moreover, a disturbed sphingolipid metabolism in the vascular wall may lead to reduced NO bioavailability and endothelial dysfunction.</description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/01.ATV.0000237569.95046.b9</identifier><identifier>PMID: 16857953</identifier><identifier>CODEN: ATVBFA</identifier><language>eng</language><publisher>Philadelphia, PA: American Heart Association, Inc</publisher><subject>Angiotensin II - pharmacology ; Animals ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Calcium - metabolism ; Cardiology. Vascular system ; Carotid Arteries - enzymology ; Carotid Arteries - metabolism ; Carotid Arteries - physiology ; Cell Line ; Coronary heart disease ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Endothelial Cells - metabolism ; Enzyme Activation - drug effects ; Enzyme Activation - physiology ; Enzyme Inhibitors - pharmacology ; Heart ; In Vitro Techniques ; Intracellular Membranes - metabolism ; Isoenzymes - metabolism ; Medical sciences ; Nitric Oxide - metabolism ; Nitric Oxide Synthase Type III - metabolism ; Osmolar Concentration ; Phosphotransferases (Alcohol Group Acceptor) - antagonists & inhibitors ; Phosphotransferases (Alcohol Group Acceptor) - metabolism ; Phosphotransferases (Alcohol Group Acceptor) - physiology ; Proto-Oncogene Proteins c-akt - physiology ; Rats ; Receptors, Lysosphingolipid - metabolism ; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis ; Vasoconstriction - drug effects ; Vasoconstrictor Agents - pharmacology</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 2006-09, Vol.26 (9), p.2043-2048</ispartof><rights>2006 American Heart Association, Inc.</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4788-8c92abdd79c79c8b9ee3d6435e3637b111144f09a2783dc1149e268b9f958c6e3</citedby><cites>FETCH-LOGICAL-c4788-8c92abdd79c79c8b9ee3d6435e3637b111144f09a2783dc1149e268b9f958c6e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18066775$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16857953$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mulders, Arthur C.M</creatorcontrib><creatorcontrib>Hendriks-Balk, Mariëlle C</creatorcontrib><creatorcontrib>Mathy, Marie-Jeanne</creatorcontrib><creatorcontrib>Michel, Martin C</creatorcontrib><creatorcontrib>Alewijnse, Astrid E</creatorcontrib><creatorcontrib>Peters, Stephan L.M</creatorcontrib><title>Sphingosine Kinase–Dependent Activation of Endothelial Nitric Oxide Synthase by Angiotensin II</title><title>Arteriosclerosis, thrombosis, and vascular biology</title><addtitle>Arterioscler Thromb Vasc Biol</addtitle><description>OBJECTIVE—In addition to their role in programmed cell death, cell survival, and cell growth, sphingolipid metabolites such as ceramide, sphingosine, and sphingosine-1-phosphate have vasoactive properties. Besides their occurrence in blood, they can also be formed locally in the vascular wall itself in response to external stimuli. This study was performed to investigate whether vasoactive compounds modulate sphingolipid metabolism in the vascular wall and how this might contribute to the vascular responses.
METHODS AND RESULTS—In isolated rat carotid arteries, the contractile responses to angiotensin II are enhanced by the sphingosine kinase inhibitor dimethylsphingosine. Endothelium removal or NO synthase inhibition by N-nitro-l-arginine results in a similar enhancement. Angiotensin II concentration-dependently induces NO production in an endothelial cell line, which can be diminished by dimethylsphingosine. Using immunoblotting and intracellular calcium measurements, we demonstrate that this sphingosine kinase–dependent endothelial NO synthase activation is mediated via both phosphatidylinositol 3-kinase/Akt and calcium-dependent pathways.
CONCLUSIONS—Angiotensin II induces a sphingosine kinase–dependent activation of endothelial NO synthase, which partially counteracts the contractile responses in isolated artery preparations. This pathway may be of importance under pathological circumstances with reduced NO bioavailability. Moreover, a disturbed sphingolipid metabolism in the vascular wall may lead to reduced NO bioavailability and endothelial dysfunction.</description><subject>Angiotensin II - pharmacology</subject><subject>Animals</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Calcium - metabolism</subject><subject>Cardiology. Vascular system</subject><subject>Carotid Arteries - enzymology</subject><subject>Carotid Arteries - metabolism</subject><subject>Carotid Arteries - physiology</subject><subject>Cell Line</subject><subject>Coronary heart disease</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Endothelial Cells - metabolism</subject><subject>Enzyme Activation - drug effects</subject><subject>Enzyme Activation - physiology</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Heart</subject><subject>In Vitro Techniques</subject><subject>Intracellular Membranes - metabolism</subject><subject>Isoenzymes - metabolism</subject><subject>Medical sciences</subject><subject>Nitric Oxide - metabolism</subject><subject>Nitric Oxide Synthase Type III - metabolism</subject><subject>Osmolar Concentration</subject><subject>Phosphotransferases (Alcohol Group Acceptor) - antagonists & inhibitors</subject><subject>Phosphotransferases (Alcohol Group Acceptor) - metabolism</subject><subject>Phosphotransferases (Alcohol Group Acceptor) - physiology</subject><subject>Proto-Oncogene Proteins c-akt - physiology</subject><subject>Rats</subject><subject>Receptors, Lysosphingolipid - metabolism</subject><subject>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</subject><subject>Vasoconstriction - drug effects</subject><subject>Vasoconstrictor Agents - pharmacology</subject><issn>1079-5642</issn><issn>1524-4636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkM9u1DAQhyNERUvhFZCFBLcEO_7PbVUKXVHRQwtX4ziTxpC1l9hL2RvvwBvyJHW7K-3Ilj3S95uRvqp6TXBDiCDvMGkWN98aXKqlkgvdaI6ZaDr9pDohvGU1E1Q8LX8sdc0Fa4-r5yn9KDxrW_ysOiZCcak5Pam-X69HH25j8gHQZx9sgv9__32ANYQeQkYLl_1vm30MKA7oPPQxjzB5O6EvPs_eoas_vgd0vQ15LFnUbdEi3PqYIZSRaLl8UR0Ndkrwcv-eVl8_nt-cXdSXV5-WZ4vL2jGpVK2cbm3X91K7clSnAWgvGOVABZUdKcXYgLVtpaK9K52GVhRu0Fw5AfS0erubu57jrw2kbFY-OZgmGyBukhFKco01KeD7HejmmNIMg1nPfmXnrSHYPPg1mJji1xz8mke_ptMl_Gq_ZdOtoD9E90IL8GYP2OTsNMw2OJ8OnMJCSMkLx3bcXZwyzOnntLmD2Yxgpzw-rGZUYF63GAusS1uXSxS9B0JjlMs</recordid><startdate>200609</startdate><enddate>200609</enddate><creator>Mulders, Arthur C.M</creator><creator>Hendriks-Balk, Mariëlle C</creator><creator>Mathy, Marie-Jeanne</creator><creator>Michel, Martin C</creator><creator>Alewijnse, Astrid E</creator><creator>Peters, Stephan L.M</creator><general>American Heart Association, Inc</general><general>Lippincott</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></search><sort><creationdate>200609</creationdate><title>Sphingosine Kinase–Dependent Activation of Endothelial Nitric Oxide Synthase by Angiotensin II</title><author>Mulders, Arthur C.M ; Hendriks-Balk, Mariëlle C ; Mathy, Marie-Jeanne ; Michel, Martin C ; Alewijnse, Astrid E ; Peters, Stephan L.M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4788-8c92abdd79c79c8b9ee3d6435e3637b111144f09a2783dc1149e268b9f958c6e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Angiotensin II - pharmacology</topic><topic>Animals</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Calcium - metabolism</topic><topic>Cardiology. Vascular system</topic><topic>Carotid Arteries - enzymology</topic><topic>Carotid Arteries - metabolism</topic><topic>Carotid Arteries - physiology</topic><topic>Cell Line</topic><topic>Coronary heart disease</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Endothelial Cells - metabolism</topic><topic>Enzyme Activation - drug effects</topic><topic>Enzyme Activation - physiology</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Heart</topic><topic>In Vitro Techniques</topic><topic>Intracellular Membranes - metabolism</topic><topic>Isoenzymes - metabolism</topic><topic>Medical sciences</topic><topic>Nitric Oxide - metabolism</topic><topic>Nitric Oxide Synthase Type III - metabolism</topic><topic>Osmolar Concentration</topic><topic>Phosphotransferases (Alcohol Group Acceptor) - antagonists & inhibitors</topic><topic>Phosphotransferases (Alcohol Group Acceptor) - metabolism</topic><topic>Phosphotransferases (Alcohol Group Acceptor) - physiology</topic><topic>Proto-Oncogene Proteins c-akt - physiology</topic><topic>Rats</topic><topic>Receptors, Lysosphingolipid - metabolism</topic><topic>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</topic><topic>Vasoconstriction - drug effects</topic><topic>Vasoconstrictor Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mulders, Arthur C.M</creatorcontrib><creatorcontrib>Hendriks-Balk, Mariëlle C</creatorcontrib><creatorcontrib>Mathy, Marie-Jeanne</creatorcontrib><creatorcontrib>Michel, Martin C</creatorcontrib><creatorcontrib>Alewijnse, Astrid E</creatorcontrib><creatorcontrib>Peters, Stephan L.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>MEDLINE - Academic</collection><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mulders, Arthur C.M</au><au>Hendriks-Balk, Mariëlle C</au><au>Mathy, Marie-Jeanne</au><au>Michel, Martin C</au><au>Alewijnse, Astrid E</au><au>Peters, Stephan L.M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sphingosine Kinase–Dependent Activation of Endothelial Nitric Oxide Synthase by Angiotensin II</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>2006-09</date><risdate>2006</risdate><volume>26</volume><issue>9</issue><spage>2043</spage><epage>2048</epage><pages>2043-2048</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><coden>ATVBFA</coden><abstract>OBJECTIVE—In addition to their role in programmed cell death, cell survival, and cell growth, sphingolipid metabolites such as ceramide, sphingosine, and sphingosine-1-phosphate have vasoactive properties. Besides their occurrence in blood, they can also be formed locally in the vascular wall itself in response to external stimuli. This study was performed to investigate whether vasoactive compounds modulate sphingolipid metabolism in the vascular wall and how this might contribute to the vascular responses.
METHODS AND RESULTS—In isolated rat carotid arteries, the contractile responses to angiotensin II are enhanced by the sphingosine kinase inhibitor dimethylsphingosine. Endothelium removal or NO synthase inhibition by N-nitro-l-arginine results in a similar enhancement. Angiotensin II concentration-dependently induces NO production in an endothelial cell line, which can be diminished by dimethylsphingosine. Using immunoblotting and intracellular calcium measurements, we demonstrate that this sphingosine kinase–dependent endothelial NO synthase activation is mediated via both phosphatidylinositol 3-kinase/Akt and calcium-dependent pathways.
CONCLUSIONS—Angiotensin II induces a sphingosine kinase–dependent activation of endothelial NO synthase, which partially counteracts the contractile responses in isolated artery preparations. This pathway may be of importance under pathological circumstances with reduced NO bioavailability. Moreover, a disturbed sphingolipid metabolism in the vascular wall may lead to reduced NO bioavailability and endothelial dysfunction.</abstract><cop>Philadelphia, PA</cop><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>16857953</pmid><doi>10.1161/01.ATV.0000237569.95046.b9</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Angiotensin II - pharmacology Animals Atherosclerosis (general aspects, experimental research) Biological and medical sciences Blood and lymphatic vessels Calcium - metabolism Cardiology. Vascular system Carotid Arteries - enzymology Carotid Arteries - metabolism Carotid Arteries - physiology Cell Line Coronary heart disease Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Endothelial Cells - metabolism Enzyme Activation - drug effects Enzyme Activation - physiology Enzyme Inhibitors - pharmacology Heart In Vitro Techniques Intracellular Membranes - metabolism Isoenzymes - metabolism Medical sciences Nitric Oxide - metabolism Nitric Oxide Synthase Type III - metabolism Osmolar Concentration Phosphotransferases (Alcohol Group Acceptor) - antagonists & inhibitors Phosphotransferases (Alcohol Group Acceptor) - metabolism Phosphotransferases (Alcohol Group Acceptor) - physiology Proto-Oncogene Proteins c-akt - physiology Rats Receptors, Lysosphingolipid - metabolism Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis Vasoconstriction - drug effects Vasoconstrictor Agents - pharmacology |
title | Sphingosine Kinase–Dependent Activation of Endothelial Nitric Oxide Synthase by Angiotensin II |
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