9-Phenanthrol, a TRPM4 inhibitor, protects isolated rat hearts from ischemia-reperfusion injury
Despite efforts to elucidate its pathophysiology, ischemia-reperfusion injury lacks an effective preventative intervention. Because transient receptor potential cation channel subfamily M member 4 (TRPM4) is functionally expressed by many cell types in the cardiovascular system and is involved in th...
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| description | Despite efforts to elucidate its pathophysiology, ischemia-reperfusion injury lacks an effective preventative intervention. Because transient receptor potential cation channel subfamily M member 4 (TRPM4) is functionally expressed by many cell types in the cardiovascular system and is involved in the pathogenesis of various cardiovascular diseases, we decided to assess its suitability as a target of therapy. Thus, the aim of this study was to examine the possible cardioprotective effect of 9-phenanthrol, a specific inhibitor of TRPM4. Isolated Langendorff-perfused rat hearts were pretreated with Krebs-Henseleit (K-H) solution (control), 9-phenanthrol, or 5-hydroxydecanoate (5-HD, a blocker of the ATP-sensitive potassium channel) and then subjected to global ischemia followed by reperfusion with the K-H solution. To evaluate the extent of heart damage, lactate dehydrogenase (LDH) activity in the effluent solution was measured, and the size of infarcted area of the heart was measured by 2,3,5-triphenyltetrazolium chloride staining. In controls, cardiac contractility decreased, and LDH activity and the infarcted area size increased. In contrast, in hearts pretreated with 9-phenanthrol, contractile function recovered dramatically, and the infarcted area size significantly decreased. The cardioprotective effects of 9-phenanthrol was not completely blocked by 5-HD. These findings show that 9-phenanthrol exerts a cardioprotective effect against ischemia in the isolated rat heart and suggest that its mechanism of action is largely independent of ATP-sensitive potassium channels. |
| doi_str_mv | 10.1371/journal.pone.0070587 |
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Because transient receptor potential cation channel subfamily M member 4 (TRPM4) is functionally expressed by many cell types in the cardiovascular system and is involved in the pathogenesis of various cardiovascular diseases, we decided to assess its suitability as a target of therapy. Thus, the aim of this study was to examine the possible cardioprotective effect of 9-phenanthrol, a specific inhibitor of TRPM4. Isolated Langendorff-perfused rat hearts were pretreated with Krebs-Henseleit (K-H) solution (control), 9-phenanthrol, or 5-hydroxydecanoate (5-HD, a blocker of the ATP-sensitive potassium channel) and then subjected to global ischemia followed by reperfusion with the K-H solution. To evaluate the extent of heart damage, lactate dehydrogenase (LDH) activity in the effluent solution was measured, and the size of infarcted area of the heart was measured by 2,3,5-triphenyltetrazolium chloride staining. In controls, cardiac contractility decreased, and LDH activity and the infarcted area size increased. In contrast, in hearts pretreated with 9-phenanthrol, contractile function recovered dramatically, and the infarcted area size significantly decreased. The cardioprotective effects of 9-phenanthrol was not completely blocked by 5-HD. These findings show that 9-phenanthrol exerts a cardioprotective effect against ischemia in the isolated rat heart and suggest that its mechanism of action is largely independent of ATP-sensitive potassium channels.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0070587</identifier><identifier>PMID: 23936231</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Anti-Arrhythmia Agents - pharmacology ; Apoptosis ; ATP ; Biology ; Biomarkers - metabolism ; Cardiology ; Cardiotonic Agents - pharmacology ; Cardiovascular disease ; Cardiovascular diseases ; Cardiovascular system ; Chlorides ; Damage assessment ; Decanoic Acids - pharmacology ; Dentistry ; Enzyme Inhibitors - pharmacology ; Glucose ; Heart ; Heart - drug effects ; Heart - physiopathology ; Heart attacks ; Heart diseases ; Hydroxy Acids - pharmacology ; In Vitro Techniques ; Inhibitors ; Injury prevention ; Ischemia ; KATP Channels - antagonists & inhibitors ; KATP Channels - metabolism ; L-Lactate dehydrogenase ; L-Lactate Dehydrogenase - metabolism ; Lactate dehydrogenase ; Lactic acid ; Male ; Medicine ; Muscle contraction ; Myocardial Contraction - drug effects ; Myocardial Reperfusion Injury - drug therapy ; Myocardial Reperfusion Injury - metabolism ; Myocardial Reperfusion Injury - physiopathology ; Pathogenesis ; Pharmaceutical sciences ; Phenanthrenes - pharmacology ; Physiology ; Potassium ; Potassium channels ; Rats ; Rats, Sprague-Dawley ; Reperfusion ; Reperfusion injury ; Rodents ; Severity of Illness Index ; Transient receptor potential proteins ; Triphenyltetrazolium chloride ; Tromethamine ; TRPM Cation Channels - antagonists & inhibitors ; TRPM Cation Channels - metabolism</subject><ispartof>PloS one, 2013-07, Vol.8 (7), p.e70587</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Wang et al 2013 Wang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-16ccf980616593a6c52048b35cef78acc508b8fbf3049f87ca1aa69f9ddce4833</citedby><cites>FETCH-LOGICAL-c758t-16ccf980616593a6c52048b35cef78acc508b8fbf3049f87ca1aa69f9ddce4833</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3723883/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3723883/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23936231$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Katare, Rajesh Gopalrao</contributor><creatorcontrib>Wang, Jing</creatorcontrib><creatorcontrib>Takahashi, Ken</creatorcontrib><creatorcontrib>Piao, Hulin</creatorcontrib><creatorcontrib>Qu, Peng</creatorcontrib><creatorcontrib>Naruse, Keiji</creatorcontrib><title>9-Phenanthrol, a TRPM4 inhibitor, protects isolated rat hearts from ischemia-reperfusion injury</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Despite efforts to elucidate its pathophysiology, ischemia-reperfusion injury lacks an effective preventative intervention. Because transient receptor potential cation channel subfamily M member 4 (TRPM4) is functionally expressed by many cell types in the cardiovascular system and is involved in the pathogenesis of various cardiovascular diseases, we decided to assess its suitability as a target of therapy. Thus, the aim of this study was to examine the possible cardioprotective effect of 9-phenanthrol, a specific inhibitor of TRPM4. Isolated Langendorff-perfused rat hearts were pretreated with Krebs-Henseleit (K-H) solution (control), 9-phenanthrol, or 5-hydroxydecanoate (5-HD, a blocker of the ATP-sensitive potassium channel) and then subjected to global ischemia followed by reperfusion with the K-H solution. To evaluate the extent of heart damage, lactate dehydrogenase (LDH) activity in the effluent solution was measured, and the size of infarcted area of the heart was measured by 2,3,5-triphenyltetrazolium chloride staining. In controls, cardiac contractility decreased, and LDH activity and the infarcted area size increased. In contrast, in hearts pretreated with 9-phenanthrol, contractile function recovered dramatically, and the infarcted area size significantly decreased. The cardioprotective effects of 9-phenanthrol was not completely blocked by 5-HD. These findings show that 9-phenanthrol exerts a cardioprotective effect against ischemia in the isolated rat heart and suggest that its mechanism of action is largely independent of ATP-sensitive potassium channels.</description><subject>Animals</subject><subject>Anti-Arrhythmia Agents - pharmacology</subject><subject>Apoptosis</subject><subject>ATP</subject><subject>Biology</subject><subject>Biomarkers - metabolism</subject><subject>Cardiology</subject><subject>Cardiotonic Agents - pharmacology</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular diseases</subject><subject>Cardiovascular system</subject><subject>Chlorides</subject><subject>Damage assessment</subject><subject>Decanoic Acids - pharmacology</subject><subject>Dentistry</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Glucose</subject><subject>Heart</subject><subject>Heart - drug effects</subject><subject>Heart - physiopathology</subject><subject>Heart attacks</subject><subject>Heart diseases</subject><subject>Hydroxy Acids - pharmacology</subject><subject>In Vitro Techniques</subject><subject>Inhibitors</subject><subject>Injury prevention</subject><subject>Ischemia</subject><subject>KATP Channels - antagonists & inhibitors</subject><subject>KATP Channels - metabolism</subject><subject>L-Lactate dehydrogenase</subject><subject>L-Lactate Dehydrogenase - metabolism</subject><subject>Lactate dehydrogenase</subject><subject>Lactic acid</subject><subject>Male</subject><subject>Medicine</subject><subject>Muscle contraction</subject><subject>Myocardial Contraction - drug effects</subject><subject>Myocardial Reperfusion Injury - drug therapy</subject><subject>Myocardial Reperfusion Injury - metabolism</subject><subject>Myocardial Reperfusion Injury - physiopathology</subject><subject>Pathogenesis</subject><subject>Pharmaceutical sciences</subject><subject>Phenanthrenes - pharmacology</subject><subject>Physiology</subject><subject>Potassium</subject><subject>Potassium channels</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reperfusion</subject><subject>Reperfusion injury</subject><subject>Rodents</subject><subject>Severity of Illness Index</subject><subject>Transient receptor potential proteins</subject><subject>Triphenyltetrazolium chloride</subject><subject>Tromethamine</subject><subject>TRPM Cation Channels - antagonists & inhibitors</subject><subject>TRPM Cation Channels - metabolism</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9tq3DAQhk1paZJt36C0hkJpId5Klq3DTSGEHhZSEtK0t0KWpbUW23IlOTRvX-2uE9YlF8UXMqNvfs38GiXJKwiWEBH4cWNH14t2OdheLQEgoKTkSXIMGcoznAP09OD_KDnxfgNAiSjGz5OjHDGEcwSPE86yq0b1og-Ns-1pKtKb66vvRWr6xlQmWHeaDs4GJYNPjbetCKpOnQhpo4SLMe1sFzdkozojMqcG5fToje2jwmZ0dy-SZ1q0Xr2c1kXy88vnm_Nv2cXl19X52UUmSUlDBrGUmlGAIS4ZEliWOShohUqpNKFCyhLQiupKI1AwTYkUUAjMNKtrqQqK0CJ5s9cdWuv55I3nsMgJhYhGJxbJak_UVmz44Ewn3B23wvBdwLo1jx0Z2SrOSlQSWQFIoSwUZkLWOa41QBhIJjWOWp-m08aqU7GEPjjRzkTnO71p-NreckRyRHflvp8EnP09Kh94F01UbSt6Zcdd3QBGM0gZ0bf_oI93N1FrERswvbbxXLkV5WcFoZQBRrZ1Lx-h4lfH65NxkLSJ8VnCh1lCZIL6E9Zi9J6vflz_P3v5a86-O2DjLLWhidM1hjg5fg4We1A6671T-sFkCPj2Hdy7wbfvgE_vIKa9Prygh6T7wUd_AeJ3AxE</recordid><startdate>20130725</startdate><enddate>20130725</enddate><creator>Wang, Jing</creator><creator>Takahashi, Ken</creator><creator>Piao, Hulin</creator><creator>Qu, Peng</creator><creator>Naruse, Keiji</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130725</creationdate><title>9-Phenanthrol, a TRPM4 inhibitor, protects isolated rat hearts from ischemia-reperfusion injury</title><author>Wang, Jing ; Takahashi, Ken ; Piao, Hulin ; Qu, Peng ; Naruse, Keiji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-16ccf980616593a6c52048b35cef78acc508b8fbf3049f87ca1aa69f9ddce4833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Anti-Arrhythmia Agents - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Jing</au><au>Takahashi, Ken</au><au>Piao, Hulin</au><au>Qu, Peng</au><au>Naruse, Keiji</au><au>Katare, Rajesh Gopalrao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>9-Phenanthrol, a TRPM4 inhibitor, protects isolated rat hearts from ischemia-reperfusion injury</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-07-25</date><risdate>2013</risdate><volume>8</volume><issue>7</issue><spage>e70587</spage><pages>e70587-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Despite efforts to elucidate its pathophysiology, ischemia-reperfusion injury lacks an effective preventative intervention. Because transient receptor potential cation channel subfamily M member 4 (TRPM4) is functionally expressed by many cell types in the cardiovascular system and is involved in the pathogenesis of various cardiovascular diseases, we decided to assess its suitability as a target of therapy. Thus, the aim of this study was to examine the possible cardioprotective effect of 9-phenanthrol, a specific inhibitor of TRPM4. Isolated Langendorff-perfused rat hearts were pretreated with Krebs-Henseleit (K-H) solution (control), 9-phenanthrol, or 5-hydroxydecanoate (5-HD, a blocker of the ATP-sensitive potassium channel) and then subjected to global ischemia followed by reperfusion with the K-H solution. To evaluate the extent of heart damage, lactate dehydrogenase (LDH) activity in the effluent solution was measured, and the size of infarcted area of the heart was measured by 2,3,5-triphenyltetrazolium chloride staining. In controls, cardiac contractility decreased, and LDH activity and the infarcted area size increased. In contrast, in hearts pretreated with 9-phenanthrol, contractile function recovered dramatically, and the infarcted area size significantly decreased. The cardioprotective effects of 9-phenanthrol was not completely blocked by 5-HD. These findings show that 9-phenanthrol exerts a cardioprotective effect against ischemia in the isolated rat heart and suggest that its mechanism of action is largely independent of ATP-sensitive potassium channels.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23936231</pmid><doi>10.1371/journal.pone.0070587</doi><tpages>e70587</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-07, Vol.8 (7), p.e70587 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1427813819 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animals Anti-Arrhythmia Agents - pharmacology Apoptosis ATP Biology Biomarkers - metabolism Cardiology Cardiotonic Agents - pharmacology Cardiovascular disease Cardiovascular diseases Cardiovascular system Chlorides Damage assessment Decanoic Acids - pharmacology Dentistry Enzyme Inhibitors - pharmacology Glucose Heart Heart - drug effects Heart - physiopathology Heart attacks Heart diseases Hydroxy Acids - pharmacology In Vitro Techniques Inhibitors Injury prevention Ischemia KATP Channels - antagonists & inhibitors KATP Channels - metabolism L-Lactate dehydrogenase L-Lactate Dehydrogenase - metabolism Lactate dehydrogenase Lactic acid Male Medicine Muscle contraction Myocardial Contraction - drug effects Myocardial Reperfusion Injury - drug therapy Myocardial Reperfusion Injury - metabolism Myocardial Reperfusion Injury - physiopathology Pathogenesis Pharmaceutical sciences Phenanthrenes - pharmacology Physiology Potassium Potassium channels Rats Rats, Sprague-Dawley Reperfusion Reperfusion injury Rodents Severity of Illness Index Transient receptor potential proteins Triphenyltetrazolium chloride Tromethamine TRPM Cation Channels - antagonists & inhibitors TRPM Cation Channels - metabolism |
| title | 9-Phenanthrol, a TRPM4 inhibitor, protects isolated rat hearts from ischemia-reperfusion injury |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-18T17%3A49%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=9-Phenanthrol,%20a%20TRPM4%20inhibitor,%20protects%20isolated%20rat%20hearts%20from%20ischemia-reperfusion%20injury&rft.jtitle=PloS%20one&rft.au=Wang,%20Jing&rft.date=2013-07-25&rft.volume=8&rft.issue=7&rft.spage=e70587&rft.pages=e70587-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0070587&rft_dat=%3Cgale_plos_%3EA478890976%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1427813819&rft_id=info:pmid/23936231&rft_galeid=A478890976&rft_doaj_id=oai_doaj_org_article_95357cb0181c4e69acd26df0360c9cf6&rfr_iscdi=true |