Androgen receptor independent cardiovascular action of the antiandrogen flutamide
We have previously shown that flutamide (specific antagonist of the androgen receptor) has antihypertensive effects. In the present study we examined the mechanisms of flutamide action in the vasculature. The vascular effects of flutamide were assayed in aortae isolated from male or female Sprague-D...
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| Veröffentlicht in: | Journal of molecular medicine (Berlin, Germany) Germany), 2003-07, Vol.81 (7), p.420-427 |
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| creator | ILIESCU, Radu CAMPOS, Luciana A SCHLEGEL, Wolfgang-Peter MORANO, Ingo BALTATU, Ovidiu BADER, Michael |
| description | We have previously shown that flutamide (specific antagonist of the androgen receptor) has antihypertensive effects. In the present study we examined the mechanisms of flutamide action in the vasculature. The vascular effects of flutamide were assayed in aortae isolated from male or female Sprague-Dawley rats and from rats or mice lacking a functional androgen receptor ( tfm, testicular feminization mutation). The effect of flutamide on coronary flow was tested in isolated hearts. In addition, male hypertensive rats with tfm mutation were treated with flutamide, and blood pressure was monitored. Flutamide induced a relaxation of rat aortae from all the strains used (maximum relaxation at 10 microM: 51.3+/-5.2% of phenylephrine contraction) and increased the coronary flow. The aortic relaxation to flutamide was abolished by endothelium removal, or by inhibition of nitric oxide synthase, guanylyl cyclase, and tyrosine kinase but not by calmodulin inhibition. Flutamide treatment attenuated the development of hypertension in mouse renin transgenic rats with the tfm mutation. Flutamide produces direct vasodilation by inducing release of NO from the endothelium and causes subsequent activation of soluble guanylyl cyclase in an active androgen receptor independent manner. This response may contribute to the observed antihypertensive actions of flutamide. |
| doi_str_mv | 10.1007/s00109-003-0449-4 |
| format | Article |
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In the present study we examined the mechanisms of flutamide action in the vasculature. The vascular effects of flutamide were assayed in aortae isolated from male or female Sprague-Dawley rats and from rats or mice lacking a functional androgen receptor ( tfm, testicular feminization mutation). The effect of flutamide on coronary flow was tested in isolated hearts. In addition, male hypertensive rats with tfm mutation were treated with flutamide, and blood pressure was monitored. Flutamide induced a relaxation of rat aortae from all the strains used (maximum relaxation at 10 microM: 51.3+/-5.2% of phenylephrine contraction) and increased the coronary flow. The aortic relaxation to flutamide was abolished by endothelium removal, or by inhibition of nitric oxide synthase, guanylyl cyclase, and tyrosine kinase but not by calmodulin inhibition. Flutamide treatment attenuated the development of hypertension in mouse renin transgenic rats with the tfm mutation. Flutamide produces direct vasodilation by inducing release of NO from the endothelium and causes subsequent activation of soluble guanylyl cyclase in an active androgen receptor independent manner. This response may contribute to the observed antihypertensive actions of flutamide.</description><identifier>ISSN: 0946-2716</identifier><identifier>EISSN: 1432-1440</identifier><identifier>DOI: 10.1007/s00109-003-0449-4</identifier><identifier>PMID: 12802502</identifier><language>eng</language><publisher>Berlin: Springer</publisher><subject>Androgen Antagonists - pharmacology ; Animals ; Animals, Genetically Modified ; Antihypertensive agents ; Antihypertensive Agents - pharmacology ; Aorta, Thoracic - drug effects ; Biological and medical sciences ; Blood Pressure - drug effects ; Cardiovascular Physiological Phenomena - drug effects ; Cardiovascular system ; Female ; Flutamide - pharmacology ; Hypertension - genetics ; Hypertension - physiopathology ; In Vitro Techniques ; Male ; Medical sciences ; Mice ; Mutation ; Pharmacology. Drug treatments ; Rats ; Rats, Long-Evans ; Rats, Sprague-Dawley ; Receptors, Androgen - genetics ; Receptors, Androgen - physiology ; Vasodilation - drug effects</subject><ispartof>Journal of molecular medicine (Berlin, Germany), 2003-07, Vol.81 (7), p.420-427</ispartof><rights>2003 INIST-CNRS</rights><rights>Copyright Springer-Verlag 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c354t-5225ce1986d898a82e7953bfdea53a2112381e5fbd163c9ae59abe87f0ea82ac3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14943078$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12802502$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ILIESCU, Radu</creatorcontrib><creatorcontrib>CAMPOS, Luciana A</creatorcontrib><creatorcontrib>SCHLEGEL, Wolfgang-Peter</creatorcontrib><creatorcontrib>MORANO, Ingo</creatorcontrib><creatorcontrib>BALTATU, Ovidiu</creatorcontrib><creatorcontrib>BADER, Michael</creatorcontrib><title>Androgen receptor independent cardiovascular action of the antiandrogen flutamide</title><title>Journal of molecular medicine (Berlin, Germany)</title><addtitle>J Mol Med (Berl)</addtitle><description>We have previously shown that flutamide (specific antagonist of the androgen receptor) has antihypertensive effects. In the present study we examined the mechanisms of flutamide action in the vasculature. The vascular effects of flutamide were assayed in aortae isolated from male or female Sprague-Dawley rats and from rats or mice lacking a functional androgen receptor ( tfm, testicular feminization mutation). The effect of flutamide on coronary flow was tested in isolated hearts. In addition, male hypertensive rats with tfm mutation were treated with flutamide, and blood pressure was monitored. Flutamide induced a relaxation of rat aortae from all the strains used (maximum relaxation at 10 microM: 51.3+/-5.2% of phenylephrine contraction) and increased the coronary flow. The aortic relaxation to flutamide was abolished by endothelium removal, or by inhibition of nitric oxide synthase, guanylyl cyclase, and tyrosine kinase but not by calmodulin inhibition. Flutamide treatment attenuated the development of hypertension in mouse renin transgenic rats with the tfm mutation. Flutamide produces direct vasodilation by inducing release of NO from the endothelium and causes subsequent activation of soluble guanylyl cyclase in an active androgen receptor independent manner. This response may contribute to the observed antihypertensive actions of flutamide.</description><subject>Androgen Antagonists - pharmacology</subject><subject>Animals</subject><subject>Animals, Genetically Modified</subject><subject>Antihypertensive agents</subject><subject>Antihypertensive Agents - pharmacology</subject><subject>Aorta, Thoracic - drug effects</subject><subject>Biological and medical sciences</subject><subject>Blood Pressure - drug effects</subject><subject>Cardiovascular Physiological Phenomena - drug effects</subject><subject>Cardiovascular system</subject><subject>Female</subject><subject>Flutamide - pharmacology</subject><subject>Hypertension - genetics</subject><subject>Hypertension - physiopathology</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mutation</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Long-Evans</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Androgen - genetics</subject><subject>Receptors, Androgen - physiology</subject><subject>Vasodilation - drug effects</subject><issn>0946-2716</issn><issn>1432-1440</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpd0E1r3DAQgGERWppt2h-QSzGF9uZmRh-WdQyhX7BQCu1ZzMrjxMErbSW7kH8fhd0S6EVzeWYQrxCXCJ8QwF4VAATXAqgWtHatPhMb1Eq2qDW8EBtwumulxe5cvC7lvmprnH4lzlH2IA3Ijfh5HYecbjk2mQMflpSbKQ584PrEpQmUhyn9pRLWmXJDYZlSbNLYLHfcUFwm-rc-zutC-2ngN-LlSHPht6d5IX5_-fzr5lu7_fH1-831tg3K6KU1UprA6Ppu6F1PvWTrjNqNA5NRJBGl6pHNuBuwU8ERG0c77u0IXDEFdSE-Hu8ecvqzcln8fiqB55kip7V4q3SnwNkK3_8H79OaY_2bl2gtgtRYER5RyKmUzKM_5GlP-cEj-KfY_hjb19j-KbbXdefd6fC62_PwvHGqW8GHE6gBaR4zxTCVZ6edVmB79QgwSIdz</recordid><startdate>20030701</startdate><enddate>20030701</enddate><creator>ILIESCU, Radu</creator><creator>CAMPOS, Luciana A</creator><creator>SCHLEGEL, Wolfgang-Peter</creator><creator>MORANO, Ingo</creator><creator>BALTATU, Ovidiu</creator><creator>BADER, Michael</creator><general>Springer</general><general>Springer Nature B.V</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>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20030701</creationdate><title>Androgen receptor independent cardiovascular action of the antiandrogen flutamide</title><author>ILIESCU, Radu ; CAMPOS, Luciana A ; SCHLEGEL, Wolfgang-Peter ; MORANO, Ingo ; BALTATU, Ovidiu ; BADER, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c354t-5225ce1986d898a82e7953bfdea53a2112381e5fbd163c9ae59abe87f0ea82ac3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Androgen Antagonists - pharmacology</topic><topic>Animals</topic><topic>Animals, Genetically Modified</topic><topic>Antihypertensive agents</topic><topic>Antihypertensive Agents - pharmacology</topic><topic>Aorta, Thoracic - drug effects</topic><topic>Biological and medical sciences</topic><topic>Blood Pressure - drug effects</topic><topic>Cardiovascular Physiological Phenomena - drug effects</topic><topic>Cardiovascular system</topic><topic>Female</topic><topic>Flutamide - pharmacology</topic><topic>Hypertension - genetics</topic><topic>Hypertension - physiopathology</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mutation</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Long-Evans</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Androgen - genetics</topic><topic>Receptors, Androgen - physiology</topic><topic>Vasodilation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ILIESCU, Radu</creatorcontrib><creatorcontrib>CAMPOS, Luciana A</creatorcontrib><creatorcontrib>SCHLEGEL, Wolfgang-Peter</creatorcontrib><creatorcontrib>MORANO, Ingo</creatorcontrib><creatorcontrib>BALTATU, Ovidiu</creatorcontrib><creatorcontrib>BADER, Michael</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>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of molecular medicine (Berlin, Germany)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ILIESCU, Radu</au><au>CAMPOS, Luciana A</au><au>SCHLEGEL, Wolfgang-Peter</au><au>MORANO, Ingo</au><au>BALTATU, Ovidiu</au><au>BADER, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Androgen receptor independent cardiovascular action of the antiandrogen flutamide</atitle><jtitle>Journal of molecular medicine (Berlin, Germany)</jtitle><addtitle>J Mol Med (Berl)</addtitle><date>2003-07-01</date><risdate>2003</risdate><volume>81</volume><issue>7</issue><spage>420</spage><epage>427</epage><pages>420-427</pages><issn>0946-2716</issn><eissn>1432-1440</eissn><abstract>We have previously shown that flutamide (specific antagonist of the androgen receptor) has antihypertensive effects. In the present study we examined the mechanisms of flutamide action in the vasculature. The vascular effects of flutamide were assayed in aortae isolated from male or female Sprague-Dawley rats and from rats or mice lacking a functional androgen receptor ( tfm, testicular feminization mutation). The effect of flutamide on coronary flow was tested in isolated hearts. In addition, male hypertensive rats with tfm mutation were treated with flutamide, and blood pressure was monitored. Flutamide induced a relaxation of rat aortae from all the strains used (maximum relaxation at 10 microM: 51.3+/-5.2% of phenylephrine contraction) and increased the coronary flow. The aortic relaxation to flutamide was abolished by endothelium removal, or by inhibition of nitric oxide synthase, guanylyl cyclase, and tyrosine kinase but not by calmodulin inhibition. Flutamide treatment attenuated the development of hypertension in mouse renin transgenic rats with the tfm mutation. Flutamide produces direct vasodilation by inducing release of NO from the endothelium and causes subsequent activation of soluble guanylyl cyclase in an active androgen receptor independent manner. This response may contribute to the observed antihypertensive actions of flutamide.</abstract><cop>Berlin</cop><pub>Springer</pub><pmid>12802502</pmid><doi>10.1007/s00109-003-0449-4</doi><tpages>8</tpages></addata></record> |
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| ispartof | Journal of molecular medicine (Berlin, Germany), 2003-07, Vol.81 (7), p.420-427 |
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| subjects | Androgen Antagonists - pharmacology Animals Animals, Genetically Modified Antihypertensive agents Antihypertensive Agents - pharmacology Aorta, Thoracic - drug effects Biological and medical sciences Blood Pressure - drug effects Cardiovascular Physiological Phenomena - drug effects Cardiovascular system Female Flutamide - pharmacology Hypertension - genetics Hypertension - physiopathology In Vitro Techniques Male Medical sciences Mice Mutation Pharmacology. Drug treatments Rats Rats, Long-Evans Rats, Sprague-Dawley Receptors, Androgen - genetics Receptors, Androgen - physiology Vasodilation - drug effects |
| title | Androgen receptor independent cardiovascular action of the antiandrogen flutamide |
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