Improvement of impaired endothelial function by tetrahydrobiopterin in stroke-prone spontaneously hypertensive rats
To investigate the role of tetrahydrobiopterin (BH4), an essential cofactor of nitric oxide synthase, in endothelial function in a model of genetic hypertension, acetylcholine- and sodium nitroprusside (SNP)-induced vasodilator responses were examined in the absence and presence of BH4 in age-matche...
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| Veröffentlicht in: | European journal of pharmacology 2010-04, Vol.631 (1), p.28-35 |
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| creator | Noguchi, Katsuhiko Hamadate, Naobumi Matsuzaki, Toshihiro Sakanashi, Mayuko Nakasone, Junko Sakanashi, Makiko Tsutsui, Masato Sakanashi, Matao |
| description | To investigate the role of tetrahydrobiopterin (BH4), an essential cofactor of nitric oxide synthase, in endothelial function in a model of genetic hypertension, acetylcholine- and sodium nitroprusside (SNP)-induced vasodilator responses were examined in the absence and presence of BH4 in age-matched adult stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats. Acetylcholine-induced depressor responses attenuated significantly in SHRSP compared with those in WKY rats. Acetylcholine-induced relaxations in phenylephrine-precontracted aortic rings of SHRSP were also significantly impaired as compared to those of WKY rats, while SNP-induced relaxations were similar between both strains. In SHRSP, intravenous infusion of BH4 (0.12
mg/kg per min for 20
min following a bolus injection of 0.48
mg/kg) significantly improved vasodilator responses to acetylcholine without affecting those to SNP, but in WKY rats BH4 did not influence those to acetylcholine. BH4 infusion itself had no hemodynamic effect in both strains. However, BH4 levels in plasma and thoracic aorta as well as plasma concentrations of nitrite plus nitrate, metabolites of NO, in SHRSP were all significantly greater than those in WKY rats, suggesting the occurrence of compensatory upregulation of NO synthesis in SHRSP. These results demonstrate that the impaired endothelial function in SHRSP cannot be explained simply by the decrease in absolute amount of BH4. |
| doi_str_mv | 10.1016/j.ejphar.2010.01.003 |
| format | Article |
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mg/kg per min for 20
min following a bolus injection of 0.48
mg/kg) significantly improved vasodilator responses to acetylcholine without affecting those to SNP, but in WKY rats BH4 did not influence those to acetylcholine. BH4 infusion itself had no hemodynamic effect in both strains. However, BH4 levels in plasma and thoracic aorta as well as plasma concentrations of nitrite plus nitrate, metabolites of NO, in SHRSP were all significantly greater than those in WKY rats, suggesting the occurrence of compensatory upregulation of NO synthesis in SHRSP. These results demonstrate that the impaired endothelial function in SHRSP cannot be explained simply by the decrease in absolute amount of BH4.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2010.01.003</identifier><identifier>PMID: 20096684</identifier><identifier>CODEN: EJPHAZ</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Acetylcholine ; Animals ; Aorta, Abdominal - drug effects ; Aorta, Abdominal - physiopathology ; Aorta, Thoracic - drug effects ; Aorta, Thoracic - metabolism ; Arterial hypertension. Arterial hypotension ; Biological and medical sciences ; Biopterins - administration & dosage ; Biopterins - analogs & derivatives ; Biopterins - blood ; Biopterins - metabolism ; Biopterins - physiology ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Dietary Supplements ; Endothelial function ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - physiopathology ; Hemodynamics - drug effects ; Hypertension - genetics ; Hypertension - physiopathology ; In Vitro Techniques ; Infusions, Intravenous ; Male ; Medical sciences ; Neurology ; Nitrates - blood ; Nitric oxide ; Nitric Oxide Synthase - antagonists & inhibitors ; Nitrites - blood ; Pharmacology. Drug treatments ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Sodium nitroprusside ; Stroke-prone spontaneously hypertensive rat ; Tetrahydrobiopterin ; Time Factors ; Vascular diseases and vascular malformations of the nervous system ; Vasoconstrictor Agents - pharmacology ; Vasodilation - drug effects ; Vasodilator Agents - pharmacology</subject><ispartof>European journal of pharmacology, 2010-04, Vol.631 (1), p.28-35</ispartof><rights>2009 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright (c) 2009 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c457t-7c970b5109d5a46455c0b995ba23e99da9aab0e8e1cedfb78a7113da66b59a5f3</citedby><cites>FETCH-LOGICAL-c457t-7c970b5109d5a46455c0b995ba23e99da9aab0e8e1cedfb78a7113da66b59a5f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014299910000403$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22610964$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20096684$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Noguchi, Katsuhiko</creatorcontrib><creatorcontrib>Hamadate, Naobumi</creatorcontrib><creatorcontrib>Matsuzaki, Toshihiro</creatorcontrib><creatorcontrib>Sakanashi, Mayuko</creatorcontrib><creatorcontrib>Nakasone, Junko</creatorcontrib><creatorcontrib>Sakanashi, Makiko</creatorcontrib><creatorcontrib>Tsutsui, Masato</creatorcontrib><creatorcontrib>Sakanashi, Matao</creatorcontrib><title>Improvement of impaired endothelial function by tetrahydrobiopterin in stroke-prone spontaneously hypertensive rats</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>To investigate the role of tetrahydrobiopterin (BH4), an essential cofactor of nitric oxide synthase, in endothelial function in a model of genetic hypertension, acetylcholine- and sodium nitroprusside (SNP)-induced vasodilator responses were examined in the absence and presence of BH4 in age-matched adult stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats. Acetylcholine-induced depressor responses attenuated significantly in SHRSP compared with those in WKY rats. Acetylcholine-induced relaxations in phenylephrine-precontracted aortic rings of SHRSP were also significantly impaired as compared to those of WKY rats, while SNP-induced relaxations were similar between both strains. In SHRSP, intravenous infusion of BH4 (0.12
mg/kg per min for 20
min following a bolus injection of 0.48
mg/kg) significantly improved vasodilator responses to acetylcholine without affecting those to SNP, but in WKY rats BH4 did not influence those to acetylcholine. BH4 infusion itself had no hemodynamic effect in both strains. However, BH4 levels in plasma and thoracic aorta as well as plasma concentrations of nitrite plus nitrate, metabolites of NO, in SHRSP were all significantly greater than those in WKY rats, suggesting the occurrence of compensatory upregulation of NO synthesis in SHRSP. These results demonstrate that the impaired endothelial function in SHRSP cannot be explained simply by the decrease in absolute amount of BH4.</description><subject>Acetylcholine</subject><subject>Animals</subject><subject>Aorta, Abdominal - drug effects</subject><subject>Aorta, Abdominal - physiopathology</subject><subject>Aorta, Thoracic - drug effects</subject><subject>Aorta, Thoracic - metabolism</subject><subject>Arterial hypertension. Arterial hypotension</subject><subject>Biological and medical sciences</subject><subject>Biopterins - administration & dosage</subject><subject>Biopterins - analogs & derivatives</subject><subject>Biopterins - blood</subject><subject>Biopterins - metabolism</subject><subject>Biopterins - physiology</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Dietary Supplements</subject><subject>Endothelial function</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - physiopathology</subject><subject>Hemodynamics - drug effects</subject><subject>Hypertension - genetics</subject><subject>Hypertension - physiopathology</subject><subject>In Vitro Techniques</subject><subject>Infusions, Intravenous</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neurology</subject><subject>Nitrates - blood</subject><subject>Nitric oxide</subject><subject>Nitric Oxide Synthase - antagonists & inhibitors</subject><subject>Nitrites - blood</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Inbred SHR</subject><subject>Rats, Inbred WKY</subject><subject>Sodium nitroprusside</subject><subject>Stroke-prone spontaneously hypertensive rat</subject><subject>Tetrahydrobiopterin</subject><subject>Time Factors</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><subject>Vasoconstrictor Agents - pharmacology</subject><subject>Vasodilation - drug effects</subject><subject>Vasodilator Agents - pharmacology</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcFq3DAQhkVoSTZp36AUXUpO3o5sy15dCiU0bSDQS3sWY3nMamtLrqRd8NtXi7ftLSAQiG9G_3zD2DsBWwGi-XjY0mHeY9iWkJ9AbAGqK7YRu1YV0IryFdsAiLoolVI37DbGAwBIVcprdlMCqKbZ1RsWn6Y5-BNN5BL3A7fTjDZQz8n1Pu1ptDjy4ehMst7xbuGJUsD90gffWT8nCtbxfGIK_hcVuZcjHmfvEjryxzgufL_MFBK5aE_EA6b4hr0ecIz09nLfsZ-PX348fCuev399evj8XJhatqlojWqhkwJUL7FuaikNdErJDsuKlOpRIXZAOxKG-qFrd9gKUfXYNJ1UKIfqjt2vfXOq30eKSU82GhrHNZpuq0qWdVnLTNYraYKPMdCg52AnDIsWoM-29UGvtvXZtgahs-1c9v7ywbGbqP9X9FdvBj5cAIwGxyGgMzb-58omT9ecuU8rR1nHyVLQ0Vhyea68C5N07-3LSf4AK7GjfA</recordid><startdate>20100410</startdate><enddate>20100410</enddate><creator>Noguchi, Katsuhiko</creator><creator>Hamadate, Naobumi</creator><creator>Matsuzaki, Toshihiro</creator><creator>Sakanashi, Mayuko</creator><creator>Nakasone, Junko</creator><creator>Sakanashi, Makiko</creator><creator>Tsutsui, Masato</creator><creator>Sakanashi, Matao</creator><general>Elsevier B.V</general><general>Elsevier</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>20100410</creationdate><title>Improvement of impaired endothelial function by tetrahydrobiopterin in stroke-prone spontaneously hypertensive rats</title><author>Noguchi, Katsuhiko ; Hamadate, Naobumi ; Matsuzaki, Toshihiro ; Sakanashi, Mayuko ; Nakasone, Junko ; Sakanashi, Makiko ; Tsutsui, Masato ; Sakanashi, Matao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c457t-7c970b5109d5a46455c0b995ba23e99da9aab0e8e1cedfb78a7113da66b59a5f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Acetylcholine</topic><topic>Animals</topic><topic>Aorta, Abdominal - drug effects</topic><topic>Aorta, Abdominal - physiopathology</topic><topic>Aorta, Thoracic - drug effects</topic><topic>Aorta, Thoracic - metabolism</topic><topic>Arterial hypertension. Arterial hypotension</topic><topic>Biological and medical sciences</topic><topic>Biopterins - administration & dosage</topic><topic>Biopterins - analogs & derivatives</topic><topic>Biopterins - blood</topic><topic>Biopterins - metabolism</topic><topic>Biopterins - physiology</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Dietary Supplements</topic><topic>Endothelial function</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - physiopathology</topic><topic>Hemodynamics - drug effects</topic><topic>Hypertension - genetics</topic><topic>Hypertension - physiopathology</topic><topic>In Vitro Techniques</topic><topic>Infusions, Intravenous</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neurology</topic><topic>Nitrates - blood</topic><topic>Nitric oxide</topic><topic>Nitric Oxide Synthase - antagonists & inhibitors</topic><topic>Nitrites - blood</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Inbred SHR</topic><topic>Rats, Inbred WKY</topic><topic>Sodium nitroprusside</topic><topic>Stroke-prone spontaneously hypertensive rat</topic><topic>Tetrahydrobiopterin</topic><topic>Time Factors</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><topic>Vasoconstrictor Agents - pharmacology</topic><topic>Vasodilation - drug effects</topic><topic>Vasodilator Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Noguchi, Katsuhiko</creatorcontrib><creatorcontrib>Hamadate, Naobumi</creatorcontrib><creatorcontrib>Matsuzaki, Toshihiro</creatorcontrib><creatorcontrib>Sakanashi, Mayuko</creatorcontrib><creatorcontrib>Nakasone, Junko</creatorcontrib><creatorcontrib>Sakanashi, Makiko</creatorcontrib><creatorcontrib>Tsutsui, Masato</creatorcontrib><creatorcontrib>Sakanashi, Matao</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>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Noguchi, Katsuhiko</au><au>Hamadate, Naobumi</au><au>Matsuzaki, Toshihiro</au><au>Sakanashi, Mayuko</au><au>Nakasone, Junko</au><au>Sakanashi, Makiko</au><au>Tsutsui, Masato</au><au>Sakanashi, Matao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improvement of impaired endothelial function by tetrahydrobiopterin in stroke-prone spontaneously hypertensive rats</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2010-04-10</date><risdate>2010</risdate><volume>631</volume><issue>1</issue><spage>28</spage><epage>35</epage><pages>28-35</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>To investigate the role of tetrahydrobiopterin (BH4), an essential cofactor of nitric oxide synthase, in endothelial function in a model of genetic hypertension, acetylcholine- and sodium nitroprusside (SNP)-induced vasodilator responses were examined in the absence and presence of BH4 in age-matched adult stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats. Acetylcholine-induced depressor responses attenuated significantly in SHRSP compared with those in WKY rats. Acetylcholine-induced relaxations in phenylephrine-precontracted aortic rings of SHRSP were also significantly impaired as compared to those of WKY rats, while SNP-induced relaxations were similar between both strains. In SHRSP, intravenous infusion of BH4 (0.12
mg/kg per min for 20
min following a bolus injection of 0.48
mg/kg) significantly improved vasodilator responses to acetylcholine without affecting those to SNP, but in WKY rats BH4 did not influence those to acetylcholine. BH4 infusion itself had no hemodynamic effect in both strains. However, BH4 levels in plasma and thoracic aorta as well as plasma concentrations of nitrite plus nitrate, metabolites of NO, in SHRSP were all significantly greater than those in WKY rats, suggesting the occurrence of compensatory upregulation of NO synthesis in SHRSP. These results demonstrate that the impaired endothelial function in SHRSP cannot be explained simply by the decrease in absolute amount of BH4.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>20096684</pmid><doi>10.1016/j.ejphar.2010.01.003</doi><tpages>8</tpages></addata></record> |
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| ispartof | European journal of pharmacology, 2010-04, Vol.631 (1), p.28-35 |
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| subjects | Acetylcholine Animals Aorta, Abdominal - drug effects Aorta, Abdominal - physiopathology Aorta, Thoracic - drug effects Aorta, Thoracic - metabolism Arterial hypertension. Arterial hypotension Biological and medical sciences Biopterins - administration & dosage Biopterins - analogs & derivatives Biopterins - blood Biopterins - metabolism Biopterins - physiology Blood and lymphatic vessels Cardiology. Vascular system Dietary Supplements Endothelial function Endothelium, Vascular - drug effects Endothelium, Vascular - physiopathology Hemodynamics - drug effects Hypertension - genetics Hypertension - physiopathology In Vitro Techniques Infusions, Intravenous Male Medical sciences Neurology Nitrates - blood Nitric oxide Nitric Oxide Synthase - antagonists & inhibitors Nitrites - blood Pharmacology. Drug treatments Rats Rats, Inbred SHR Rats, Inbred WKY Sodium nitroprusside Stroke-prone spontaneously hypertensive rat Tetrahydrobiopterin Time Factors Vascular diseases and vascular malformations of the nervous system Vasoconstrictor Agents - pharmacology Vasodilation - drug effects Vasodilator Agents - pharmacology |
| title | Improvement of impaired endothelial function by tetrahydrobiopterin in stroke-prone spontaneously hypertensive rats |
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