Effects of fasudil, a Rho-kinase inhibitor, on myocardial preconditioning in anesthetized rats
The aim of this study was to examine the effects of fasudil, a Rho-kinase inhibitor, on ischemic preconditioning and carbachol preconditioning in anesthetized rats. The total number of ventricular ectopic beats was markedly augmented with fasudil at 0.3 mg/kg and depressed with fasudil at 10 mg/kg....
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| Veröffentlicht in: | European journal of pharmacology 2005-12, Vol.527 (1), p.129-140 |
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| creator | Demiryürek, Şeniz Kara, Ali F. Çelik, Ahmet Babül, Aydan Tarakçıogˇlu, Mehmet Demiryürek, Abdullah T. |
| description | The aim of this study was to examine the effects of fasudil, a Rho-kinase inhibitor, on ischemic preconditioning and carbachol preconditioning in anesthetized rats. The total number of ventricular ectopic beats was markedly augmented with fasudil at 0.3 mg/kg and depressed with fasudil at 10 mg/kg. Fasudil at 10 mg/kg also markedly decreased the ventricular tachycardia incidence. Ischemic preconditioning, induced by 5 min coronary artery occlusion and 5 min reperfusion, decreased the incidence of ventricular tachycardia and abolished the occurrence of ventricular fibrillation. The incidences of ventricular tachycardia and ventricular fibrillation in the fasudil (10 mg/kg)
+
ischemic preconditioning group were found to be similar to the ischemic preconditioning group. However, low doses of fasudil (0.3 and 1 mg/kg) appeared to prevent the antiarrhythmic effects of ischemic preconditioning. Carbachol (4 μg/kg/min for 5 min) induced marked reductions in mean arterial blood pressure, heart rate and abolished ventricular tachycardia. Marked reductions in ventricular ectopic beats and ventricular tachycardia were noted in the fasudil (10 mg/kg)
+
carbachol preconditioning group. Lactate levels were markedly reduced in the ischemic preconditioning group and this reduction was prominently inhibited with fasudil at 1 mg/kg. Ischemic preconditioning caused a marked decrease in plasma malondialdehyde levels. Fasudil (10 mg/kg), ischemic preconditioning and carbachol preconditioning each generated marked reductions in ischemic myocardial malondialdehyde levels. Decreases in infarct size were observed with fasudil (10 mg/kg) treatment, ischemic preconditioning and carbachol preconditioning when compared to control. These results suggest that low doses of fasudil (0.3 and 1 mg/kg) appeared to prevents the effects of ischemic preconditioning and carbachol preconditioning, but a high dose of fasudil (10 mg/kg) was able to produce cardioprotective effects on myocardium against arrhythmias, infarct size or biochemical parameters and mimic the effects of ischemic preconditioning in anesthetized rats. |
| doi_str_mv | 10.1016/j.ejphar.2005.10.018 |
| format | Article |
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+
ischemic preconditioning group were found to be similar to the ischemic preconditioning group. However, low doses of fasudil (0.3 and 1 mg/kg) appeared to prevent the antiarrhythmic effects of ischemic preconditioning. Carbachol (4 μg/kg/min for 5 min) induced marked reductions in mean arterial blood pressure, heart rate and abolished ventricular tachycardia. Marked reductions in ventricular ectopic beats and ventricular tachycardia were noted in the fasudil (10 mg/kg)
+
carbachol preconditioning group. Lactate levels were markedly reduced in the ischemic preconditioning group and this reduction was prominently inhibited with fasudil at 1 mg/kg. Ischemic preconditioning caused a marked decrease in plasma malondialdehyde levels. Fasudil (10 mg/kg), ischemic preconditioning and carbachol preconditioning each generated marked reductions in ischemic myocardial malondialdehyde levels. Decreases in infarct size were observed with fasudil (10 mg/kg) treatment, ischemic preconditioning and carbachol preconditioning when compared to control. These results suggest that low doses of fasudil (0.3 and 1 mg/kg) appeared to prevents the effects of ischemic preconditioning and carbachol preconditioning, but a high dose of fasudil (10 mg/kg) was able to produce cardioprotective effects on myocardium against arrhythmias, infarct size or biochemical parameters and mimic the effects of ischemic preconditioning in anesthetized rats.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2005.10.018</identifier><identifier>PMID: 16307738</identifier><identifier>CODEN: EJPHAZ</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives ; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology ; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - therapeutic use ; Anesthesia ; Animals ; Arrhythmia ; Biological and medical sciences ; Blood Pressure - drug effects ; Carbachol - pharmacology ; Carbachol - therapeutic use ; Cardiac dysrhythmias ; Cardiology. Vascular system ; Cardiotonic Agents - pharmacology ; Cardiotonic Agents - therapeutic use ; Coronary Vessels - drug effects ; Coronary Vessels - physiopathology ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drug Therapy, Combination ; Fasudil ; Heart ; Infarct size ; Intracellular Signaling Peptides and Proteins ; Ischemic Preconditioning, Myocardial - adverse effects ; Ischemic Preconditioning, Myocardial - methods ; Lactates - blood ; Male ; Malondialdehyde - blood ; Medical sciences ; Myocardial Infarction - blood ; Myocardial Infarction - drug therapy ; Myocardial Infarction - physiopathology ; Neutrophils - drug effects ; Neutrophils - metabolism ; Pharmacology. Drug treatments ; Preconditioning ; Protein-Serine-Threonine Kinases - antagonists & inhibitors ; Protein-Serine-Threonine Kinases - metabolism ; Rats ; Rats, Wistar ; rho-Associated Kinases ; Rho-kinase ; Tachycardia, Ventricular - drug therapy ; Tachycardia, Ventricular - etiology ; Tachycardia, Ventricular - physiopathology ; Vasodilation - drug effects ; Ventricular Premature Complexes - drug therapy ; Ventricular Premature Complexes - etiology ; Ventricular Premature Complexes - physiopathology</subject><ispartof>European journal of pharmacology, 2005-12, Vol.527 (1), p.129-140</ispartof><rights>2005 Elsevier B.V.</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-ac2568ed5540f8e93f03140b770aedd7cef01648a073f1e639a4ae7070fdcf203</citedby><cites>FETCH-LOGICAL-c456t-ac2568ed5540f8e93f03140b770aedd7cef01648a073f1e639a4ae7070fdcf203</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejphar.2005.10.018$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17322949$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16307738$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Demiryürek, Şeniz</creatorcontrib><creatorcontrib>Kara, Ali F.</creatorcontrib><creatorcontrib>Çelik, Ahmet</creatorcontrib><creatorcontrib>Babül, Aydan</creatorcontrib><creatorcontrib>Tarakçıogˇlu, Mehmet</creatorcontrib><creatorcontrib>Demiryürek, Abdullah T.</creatorcontrib><title>Effects of fasudil, a Rho-kinase inhibitor, on myocardial preconditioning in anesthetized rats</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>The aim of this study was to examine the effects of fasudil, a Rho-kinase inhibitor, on ischemic preconditioning and carbachol preconditioning in anesthetized rats. The total number of ventricular ectopic beats was markedly augmented with fasudil at 0.3 mg/kg and depressed with fasudil at 10 mg/kg. Fasudil at 10 mg/kg also markedly decreased the ventricular tachycardia incidence. Ischemic preconditioning, induced by 5 min coronary artery occlusion and 5 min reperfusion, decreased the incidence of ventricular tachycardia and abolished the occurrence of ventricular fibrillation. The incidences of ventricular tachycardia and ventricular fibrillation in the fasudil (10 mg/kg)
+
ischemic preconditioning group were found to be similar to the ischemic preconditioning group. However, low doses of fasudil (0.3 and 1 mg/kg) appeared to prevent the antiarrhythmic effects of ischemic preconditioning. Carbachol (4 μg/kg/min for 5 min) induced marked reductions in mean arterial blood pressure, heart rate and abolished ventricular tachycardia. Marked reductions in ventricular ectopic beats and ventricular tachycardia were noted in the fasudil (10 mg/kg)
+
carbachol preconditioning group. Lactate levels were markedly reduced in the ischemic preconditioning group and this reduction was prominently inhibited with fasudil at 1 mg/kg. Ischemic preconditioning caused a marked decrease in plasma malondialdehyde levels. Fasudil (10 mg/kg), ischemic preconditioning and carbachol preconditioning each generated marked reductions in ischemic myocardial malondialdehyde levels. Decreases in infarct size were observed with fasudil (10 mg/kg) treatment, ischemic preconditioning and carbachol preconditioning when compared to control. These results suggest that low doses of fasudil (0.3 and 1 mg/kg) appeared to prevents the effects of ischemic preconditioning and carbachol preconditioning, but a high dose of fasudil (10 mg/kg) was able to produce cardioprotective effects on myocardium against arrhythmias, infarct size or biochemical parameters and mimic the effects of ischemic preconditioning in anesthetized rats.</description><subject>1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives</subject><subject>1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology</subject><subject>1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - therapeutic use</subject><subject>Anesthesia</subject><subject>Animals</subject><subject>Arrhythmia</subject><subject>Biological and medical sciences</subject><subject>Blood Pressure - drug effects</subject><subject>Carbachol - pharmacology</subject><subject>Carbachol - therapeutic use</subject><subject>Cardiac dysrhythmias</subject><subject>Cardiology. Vascular system</subject><subject>Cardiotonic Agents - pharmacology</subject><subject>Cardiotonic Agents - therapeutic use</subject><subject>Coronary Vessels - drug effects</subject><subject>Coronary Vessels - physiopathology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Administration Schedule</subject><subject>Drug Therapy, Combination</subject><subject>Fasudil</subject><subject>Heart</subject><subject>Infarct size</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>Ischemic Preconditioning, Myocardial - adverse effects</subject><subject>Ischemic Preconditioning, Myocardial - methods</subject><subject>Lactates - blood</subject><subject>Male</subject><subject>Malondialdehyde - blood</subject><subject>Medical sciences</subject><subject>Myocardial Infarction - blood</subject><subject>Myocardial Infarction - drug therapy</subject><subject>Myocardial Infarction - physiopathology</subject><subject>Neutrophils - drug effects</subject><subject>Neutrophils - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Preconditioning</subject><subject>Protein-Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>rho-Associated Kinases</subject><subject>Rho-kinase</subject><subject>Tachycardia, Ventricular - drug therapy</subject><subject>Tachycardia, Ventricular - etiology</subject><subject>Tachycardia, Ventricular - physiopathology</subject><subject>Vasodilation - drug effects</subject><subject>Ventricular Premature Complexes - drug therapy</subject><subject>Ventricular Premature Complexes - etiology</subject><subject>Ventricular Premature Complexes - physiopathology</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1rGzEQhkVJaJyk_6AEXdJT1h3tl1aXQAhpGggUSnOtGEujWs5acqR1IP31lbEht54Ghmdm3nkY-yxgLkD0X1dzWm2WmOY1QFdacxDDBzYTg1QVSFEfsRmAaKtaKXXCTnNeQQFV3X1kJ6JvQMpmmLHfd86RmTKPjjvMW-vHK4785zJWzz5gJu7D0i_8FNMVj4Gv36LBZD2OfJPIxGD95GPw4U8BOQbK05Im_5csTzjlc3bscMz06VDP2NO3u1-336vHH_cPtzePlWm7fqrQ1F0_kO26FtxAqnHQiBYWUgKStdKQKy-3A4JsnKC-UdgiSZDgrHE1NGfsy37vJsWXbQmh1z4bGseSKG6z7oehUxJUAds9aFLMOZHTm-TXmN60AL3zqld671XvvO66xWsZuzjs3y7WZN-HDiILcHkAMBscXcJgfH7nZFPXqt3dv95zVGy8eko6G0_BkPVF56Rt9P9P8g_JJpjb</recordid><startdate>20051219</startdate><enddate>20051219</enddate><creator>Demiryürek, Şeniz</creator><creator>Kara, Ali F.</creator><creator>Çelik, Ahmet</creator><creator>Babül, Aydan</creator><creator>Tarakçıogˇlu, Mehmet</creator><creator>Demiryürek, Abdullah T.</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>20051219</creationdate><title>Effects of fasudil, a Rho-kinase inhibitor, on myocardial preconditioning in anesthetized rats</title><author>Demiryürek, Şeniz ; Kara, Ali F. ; Çelik, Ahmet ; Babül, Aydan ; Tarakçıogˇlu, Mehmet ; Demiryürek, Abdullah T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-ac2568ed5540f8e93f03140b770aedd7cef01648a073f1e639a4ae7070fdcf203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives</topic><topic>1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology</topic><topic>1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - therapeutic use</topic><topic>Anesthesia</topic><topic>Animals</topic><topic>Arrhythmia</topic><topic>Biological and medical sciences</topic><topic>Blood Pressure - drug effects</topic><topic>Carbachol - pharmacology</topic><topic>Carbachol - therapeutic use</topic><topic>Cardiac dysrhythmias</topic><topic>Cardiology. Vascular system</topic><topic>Cardiotonic Agents - pharmacology</topic><topic>Cardiotonic Agents - therapeutic use</topic><topic>Coronary Vessels - drug effects</topic><topic>Coronary Vessels - physiopathology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Administration Schedule</topic><topic>Drug Therapy, Combination</topic><topic>Fasudil</topic><topic>Heart</topic><topic>Infarct size</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>Ischemic Preconditioning, Myocardial - adverse effects</topic><topic>Ischemic Preconditioning, Myocardial - methods</topic><topic>Lactates - blood</topic><topic>Male</topic><topic>Malondialdehyde - blood</topic><topic>Medical sciences</topic><topic>Myocardial Infarction - blood</topic><topic>Myocardial Infarction - drug therapy</topic><topic>Myocardial Infarction - physiopathology</topic><topic>Neutrophils - drug effects</topic><topic>Neutrophils - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Preconditioning</topic><topic>Protein-Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>rho-Associated Kinases</topic><topic>Rho-kinase</topic><topic>Tachycardia, Ventricular - drug therapy</topic><topic>Tachycardia, Ventricular - etiology</topic><topic>Tachycardia, Ventricular - physiopathology</topic><topic>Vasodilation - drug effects</topic><topic>Ventricular Premature Complexes - drug therapy</topic><topic>Ventricular Premature Complexes - etiology</topic><topic>Ventricular Premature Complexes - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Demiryürek, Şeniz</creatorcontrib><creatorcontrib>Kara, Ali F.</creatorcontrib><creatorcontrib>Çelik, Ahmet</creatorcontrib><creatorcontrib>Babül, Aydan</creatorcontrib><creatorcontrib>Tarakçıogˇlu, Mehmet</creatorcontrib><creatorcontrib>Demiryürek, Abdullah T.</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>Demiryürek, Şeniz</au><au>Kara, Ali F.</au><au>Çelik, Ahmet</au><au>Babül, Aydan</au><au>Tarakçıogˇlu, Mehmet</au><au>Demiryürek, Abdullah T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of fasudil, a Rho-kinase inhibitor, on myocardial preconditioning in anesthetized rats</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2005-12-19</date><risdate>2005</risdate><volume>527</volume><issue>1</issue><spage>129</spage><epage>140</epage><pages>129-140</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>The aim of this study was to examine the effects of fasudil, a Rho-kinase inhibitor, on ischemic preconditioning and carbachol preconditioning in anesthetized rats. The total number of ventricular ectopic beats was markedly augmented with fasudil at 0.3 mg/kg and depressed with fasudil at 10 mg/kg. Fasudil at 10 mg/kg also markedly decreased the ventricular tachycardia incidence. Ischemic preconditioning, induced by 5 min coronary artery occlusion and 5 min reperfusion, decreased the incidence of ventricular tachycardia and abolished the occurrence of ventricular fibrillation. The incidences of ventricular tachycardia and ventricular fibrillation in the fasudil (10 mg/kg)
+
ischemic preconditioning group were found to be similar to the ischemic preconditioning group. However, low doses of fasudil (0.3 and 1 mg/kg) appeared to prevent the antiarrhythmic effects of ischemic preconditioning. Carbachol (4 μg/kg/min for 5 min) induced marked reductions in mean arterial blood pressure, heart rate and abolished ventricular tachycardia. Marked reductions in ventricular ectopic beats and ventricular tachycardia were noted in the fasudil (10 mg/kg)
+
carbachol preconditioning group. Lactate levels were markedly reduced in the ischemic preconditioning group and this reduction was prominently inhibited with fasudil at 1 mg/kg. Ischemic preconditioning caused a marked decrease in plasma malondialdehyde levels. Fasudil (10 mg/kg), ischemic preconditioning and carbachol preconditioning each generated marked reductions in ischemic myocardial malondialdehyde levels. Decreases in infarct size were observed with fasudil (10 mg/kg) treatment, ischemic preconditioning and carbachol preconditioning when compared to control. These results suggest that low doses of fasudil (0.3 and 1 mg/kg) appeared to prevents the effects of ischemic preconditioning and carbachol preconditioning, but a high dose of fasudil (10 mg/kg) was able to produce cardioprotective effects on myocardium against arrhythmias, infarct size or biochemical parameters and mimic the effects of ischemic preconditioning in anesthetized rats.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>16307738</pmid><doi>10.1016/j.ejphar.2005.10.018</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | European journal of pharmacology, 2005-12, Vol.527 (1), p.129-140 |
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| subjects | 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - therapeutic use Anesthesia Animals Arrhythmia Biological and medical sciences Blood Pressure - drug effects Carbachol - pharmacology Carbachol - therapeutic use Cardiac dysrhythmias Cardiology. Vascular system Cardiotonic Agents - pharmacology Cardiotonic Agents - therapeutic use Coronary Vessels - drug effects Coronary Vessels - physiopathology Dose-Response Relationship, Drug Drug Administration Schedule Drug Therapy, Combination Fasudil Heart Infarct size Intracellular Signaling Peptides and Proteins Ischemic Preconditioning, Myocardial - adverse effects Ischemic Preconditioning, Myocardial - methods Lactates - blood Male Malondialdehyde - blood Medical sciences Myocardial Infarction - blood Myocardial Infarction - drug therapy Myocardial Infarction - physiopathology Neutrophils - drug effects Neutrophils - metabolism Pharmacology. Drug treatments Preconditioning Protein-Serine-Threonine Kinases - antagonists & inhibitors Protein-Serine-Threonine Kinases - metabolism Rats Rats, Wistar rho-Associated Kinases Rho-kinase Tachycardia, Ventricular - drug therapy Tachycardia, Ventricular - etiology Tachycardia, Ventricular - physiopathology Vasodilation - drug effects Ventricular Premature Complexes - drug therapy Ventricular Premature Complexes - etiology Ventricular Premature Complexes - physiopathology |
| title | Effects of fasudil, a Rho-kinase inhibitor, on myocardial preconditioning in anesthetized rats |
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