The Hepatic Soluble Guanylyl Cyclase-Cyclic Guanosine Monophosphate Pathway Mediates the Protection of Remote Ischemic Preconditioning on the Microcirculation in Liver Ischemia-Reperfusion Injury
Remote ischemic preconditioning (RIPC) protects against liver ischemia reperfusion (IR) injury. An essential circulating mediator of this protection is nitric oxide (NO) induced by lower limb RIPC. One of the mechanisms through which NO generally acts is the soluble guanylyl cyclase-cyclic GMP (sGC-...
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| Veröffentlicht in: | Transplantation 2012-05, Vol.93 (9), p.880-886 |
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| creator | ABU-AMARA, Mahmoud YANG, Shi Y QUAGLIA, Alberto ROWLEY, Peter TAPURIA, Niteen FULLER, Barry DAVIDSON, Brian SEIFALIAN, Alexander |
| description | Remote ischemic preconditioning (RIPC) protects against liver ischemia reperfusion (IR) injury. An essential circulating mediator of this protection is nitric oxide (NO) induced by lower limb RIPC. One of the mechanisms through which NO generally acts is the soluble guanylyl cyclase-cyclic GMP (sGC-cGMP) pathway. The present study aimed to assess the role of hepatic sGC-cGMP in lower limb RIPC-induced protection against liver IR injury.
Mice were allocated to 4 groups: 1.Sham; 2.IR: 40 min of lobar hepatic ischemia and 2 hr reperfusion; 3.RIPC+IR: 6 cycles of 4x4 min IR of the lower limb followed by IR group procedure; (4) 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ)+RIPC+IR: ODQ (sGC inhibitor) was administered followed by RIPC+IR group procedure. Hepatic microcirculatory blood flow (MBF) was measured throughout the experiment. Plasma transaminases, hepatic histopathological and transmission electron microscopy studies were performed at the end of the experiment. Hepatic cGMP levels were measured in groups 1-3 in addition to an RIPC alone group.
Compared to liver IR alone, RIPC+IR increased hepatic MBF during liver reperfusion (P |
| doi_str_mv | 10.1097/TP.0b013e31824cd59d |
| format | Article |
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Mice were allocated to 4 groups: 1.Sham; 2.IR: 40 min of lobar hepatic ischemia and 2 hr reperfusion; 3.RIPC+IR: 6 cycles of 4x4 min IR of the lower limb followed by IR group procedure; (4) 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ)+RIPC+IR: ODQ (sGC inhibitor) was administered followed by RIPC+IR group procedure. Hepatic microcirculatory blood flow (MBF) was measured throughout the experiment. Plasma transaminases, hepatic histopathological and transmission electron microscopy studies were performed at the end of the experiment. Hepatic cGMP levels were measured in groups 1-3 in addition to an RIPC alone group.
Compared to liver IR alone, RIPC+IR increased hepatic MBF during liver reperfusion (P<0.05), and reduced plasma transaminases (P<0.05) and ultrastructural markers of injury. In contrast compared to RIPC+IR, ODQ+RIPC+IR decreased hepatic MBF (P<0.05) and ultrastructural markers of injury. However, plasma transaminases were not significantly different in the ODQ+RIPC+IR compared to the RIPC+IR group. Hepatic cGMP levels were significantly elevated in the RIPC compared to sham group.
The hepatic sGC-cGMP pathway is required for mediating the protective effects of lower limb RIPC on hepatic MBF in liver IR injury.</description><identifier>ISSN: 0041-1337</identifier><identifier>EISSN: 1534-6080</identifier><identifier>DOI: 10.1097/TP.0b013e31824cd59d</identifier><identifier>PMID: 22456530</identifier><identifier>CODEN: TRPLAU</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Animals ; Biological and medical sciences ; Cyclic GMP ; Cyclic GMP - metabolism ; Disease Models, Animal ; Follow-Up Studies ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Gastroenterology. Liver. Pancreas. Abdomen ; Guanosine ; Guanylate Cyclase - metabolism ; Injuries ; Ischemia ; Ischemic Preconditioning - methods ; Limbs ; Liver ; Liver - blood supply ; Liver - metabolism ; Liver - ultrastructure ; Liver Circulation - physiology ; Liver Diseases - metabolism ; Liver Diseases - physiopathology ; Liver Diseases - prevention & control ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Medical sciences ; Mice ; Microcirculation - physiology ; Microscopy, Electron, Transmission ; Nitric oxide ; Other diseases. Semiology ; Receptors, Cytoplasmic and Nuclear - metabolism ; Reperfusion ; Reperfusion Injury - metabolism ; Reperfusion Injury - pathology ; Reperfusion Injury - prevention & control ; Soluble Guanylyl Cyclase ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Tissue, organ and graft immunology ; transaminase ; Transmission electron microscopy</subject><ispartof>Transplantation, 2012-05, Vol.93 (9), p.880-886</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c413t-2344396e302fb46cafc755db1ca59dfc0acfbc54e6c3b3742700c2435e6896c63</citedby><cites>FETCH-LOGICAL-c413t-2344396e302fb46cafc755db1ca59dfc0acfbc54e6c3b3742700c2435e6896c63</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=25873006$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22456530$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ABU-AMARA, Mahmoud</creatorcontrib><creatorcontrib>YANG, Shi Y</creatorcontrib><creatorcontrib>QUAGLIA, Alberto</creatorcontrib><creatorcontrib>ROWLEY, Peter</creatorcontrib><creatorcontrib>TAPURIA, Niteen</creatorcontrib><creatorcontrib>FULLER, Barry</creatorcontrib><creatorcontrib>DAVIDSON, Brian</creatorcontrib><creatorcontrib>SEIFALIAN, Alexander</creatorcontrib><title>The Hepatic Soluble Guanylyl Cyclase-Cyclic Guanosine Monophosphate Pathway Mediates the Protection of Remote Ischemic Preconditioning on the Microcirculation in Liver Ischemia-Reperfusion Injury</title><title>Transplantation</title><addtitle>Transplantation</addtitle><description>Remote ischemic preconditioning (RIPC) protects against liver ischemia reperfusion (IR) injury. An essential circulating mediator of this protection is nitric oxide (NO) induced by lower limb RIPC. One of the mechanisms through which NO generally acts is the soluble guanylyl cyclase-cyclic GMP (sGC-cGMP) pathway. The present study aimed to assess the role of hepatic sGC-cGMP in lower limb RIPC-induced protection against liver IR injury.
Mice were allocated to 4 groups: 1.Sham; 2.IR: 40 min of lobar hepatic ischemia and 2 hr reperfusion; 3.RIPC+IR: 6 cycles of 4x4 min IR of the lower limb followed by IR group procedure; (4) 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ)+RIPC+IR: ODQ (sGC inhibitor) was administered followed by RIPC+IR group procedure. Hepatic microcirculatory blood flow (MBF) was measured throughout the experiment. Plasma transaminases, hepatic histopathological and transmission electron microscopy studies were performed at the end of the experiment. Hepatic cGMP levels were measured in groups 1-3 in addition to an RIPC alone group.
Compared to liver IR alone, RIPC+IR increased hepatic MBF during liver reperfusion (P<0.05), and reduced plasma transaminases (P<0.05) and ultrastructural markers of injury. In contrast compared to RIPC+IR, ODQ+RIPC+IR decreased hepatic MBF (P<0.05) and ultrastructural markers of injury. However, plasma transaminases were not significantly different in the ODQ+RIPC+IR compared to the RIPC+IR group. Hepatic cGMP levels were significantly elevated in the RIPC compared to sham group.
The hepatic sGC-cGMP pathway is required for mediating the protective effects of lower limb RIPC on hepatic MBF in liver IR injury.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cyclic GMP</subject><subject>Cyclic GMP - metabolism</subject><subject>Disease Models, Animal</subject><subject>Follow-Up Studies</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Guanosine</subject><subject>Guanylate Cyclase - metabolism</subject><subject>Injuries</subject><subject>Ischemia</subject><subject>Ischemic Preconditioning - methods</subject><subject>Limbs</subject><subject>Liver</subject><subject>Liver - blood supply</subject><subject>Liver - metabolism</subject><subject>Liver - ultrastructure</subject><subject>Liver Circulation - physiology</subject><subject>Liver Diseases - metabolism</subject><subject>Liver Diseases - physiopathology</subject><subject>Liver Diseases - prevention & control</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Microcirculation - physiology</subject><subject>Microscopy, Electron, Transmission</subject><subject>Nitric oxide</subject><subject>Other diseases. Semiology</subject><subject>Receptors, Cytoplasmic and Nuclear - metabolism</subject><subject>Reperfusion</subject><subject>Reperfusion Injury - metabolism</subject><subject>Reperfusion Injury - pathology</subject><subject>Reperfusion Injury - prevention & control</subject><subject>Soluble Guanylyl Cyclase</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Tissue, organ and graft immunology</subject><subject>transaminase</subject><subject>Transmission electron microscopy</subject><issn>0041-1337</issn><issn>1534-6080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUGP0zAQhS0EYkvhFyAhX5C4ZLEzdtIeUbXsVmpFtZRz5Ewm1KskDnYCyu_bP7YO2wWJE6fR-H3vWfZj7K0Ul1Ks84_Hw6UohQQCuUoVVnpdPWMLqUElmViJ52whhJKJBMgv2KsQ7oQQGvL8JbtIU6UzDWLB7o8n4jfUm8Ei_-qasWyIX4-mm5qp4ZsJGxMomWfU53MXbEd87zrXn1zoT2YgfjDD6ZeZ-J4qG_fAhxh68G4gHKzruKv5LbVx5duAJ2pj1METuq6ys2677zxSs2lv0Tu0HsfG_Lbaju_sT_JPTpPcUk--HsOsbru70U-v2YvaNIHenOeSfft8ddzcJLsv19vNp12CSsKQpKAUrDMCkdalytDUmGtdlRJN_LoahcG6RK0oQyghV2kuBKYKNGWrdYYZLNmHx9zeux8jhaFobUBqGtORG0MhBawyKSWs_wOVIgUtY1tLBo9ofHkInuqi97Y1fopQMRddHA_Fv0VH17vzBWPZUvXH89RsBN6fARPQNLU3Hdrwl9OrHITI4AE9J7Zu</recordid><startdate>20120515</startdate><enddate>20120515</enddate><creator>ABU-AMARA, Mahmoud</creator><creator>YANG, Shi Y</creator><creator>QUAGLIA, Alberto</creator><creator>ROWLEY, Peter</creator><creator>TAPURIA, Niteen</creator><creator>FULLER, Barry</creator><creator>DAVIDSON, Brian</creator><creator>SEIFALIAN, Alexander</creator><general>Lippincott Williams & Wilkins</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><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>20120515</creationdate><title>The Hepatic Soluble Guanylyl Cyclase-Cyclic Guanosine Monophosphate Pathway Mediates the Protection of Remote Ischemic Preconditioning on the Microcirculation in Liver Ischemia-Reperfusion Injury</title><author>ABU-AMARA, Mahmoud ; YANG, Shi Y ; QUAGLIA, Alberto ; ROWLEY, Peter ; TAPURIA, Niteen ; FULLER, Barry ; DAVIDSON, Brian ; SEIFALIAN, Alexander</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c413t-2344396e302fb46cafc755db1ca59dfc0acfbc54e6c3b3742700c2435e6896c63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cyclic GMP</topic><topic>Cyclic GMP - metabolism</topic><topic>Disease Models, Animal</topic><topic>Follow-Up Studies</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Guanosine</topic><topic>Guanylate Cyclase - metabolism</topic><topic>Injuries</topic><topic>Ischemia</topic><topic>Ischemic Preconditioning - methods</topic><topic>Limbs</topic><topic>Liver</topic><topic>Liver - blood supply</topic><topic>Liver - metabolism</topic><topic>Liver - ultrastructure</topic><topic>Liver Circulation - physiology</topic><topic>Liver Diseases - metabolism</topic><topic>Liver Diseases - physiopathology</topic><topic>Liver Diseases - prevention & control</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Microcirculation - physiology</topic><topic>Microscopy, Electron, Transmission</topic><topic>Nitric oxide</topic><topic>Other diseases. Semiology</topic><topic>Receptors, Cytoplasmic and Nuclear - metabolism</topic><topic>Reperfusion</topic><topic>Reperfusion Injury - metabolism</topic><topic>Reperfusion Injury - pathology</topic><topic>Reperfusion Injury - prevention & control</topic><topic>Soluble Guanylyl Cyclase</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Tissue, organ and graft immunology</topic><topic>transaminase</topic><topic>Transmission electron microscopy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ABU-AMARA, Mahmoud</creatorcontrib><creatorcontrib>YANG, Shi Y</creatorcontrib><creatorcontrib>QUAGLIA, Alberto</creatorcontrib><creatorcontrib>ROWLEY, Peter</creatorcontrib><creatorcontrib>TAPURIA, Niteen</creatorcontrib><creatorcontrib>FULLER, Barry</creatorcontrib><creatorcontrib>DAVIDSON, Brian</creatorcontrib><creatorcontrib>SEIFALIAN, Alexander</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><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ABU-AMARA, Mahmoud</au><au>YANG, Shi Y</au><au>QUAGLIA, Alberto</au><au>ROWLEY, Peter</au><au>TAPURIA, Niteen</au><au>FULLER, Barry</au><au>DAVIDSON, Brian</au><au>SEIFALIAN, Alexander</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Hepatic Soluble Guanylyl Cyclase-Cyclic Guanosine Monophosphate Pathway Mediates the Protection of Remote Ischemic Preconditioning on the Microcirculation in Liver Ischemia-Reperfusion Injury</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>2012-05-15</date><risdate>2012</risdate><volume>93</volume><issue>9</issue><spage>880</spage><epage>886</epage><pages>880-886</pages><issn>0041-1337</issn><eissn>1534-6080</eissn><coden>TRPLAU</coden><abstract>Remote ischemic preconditioning (RIPC) protects against liver ischemia reperfusion (IR) injury. An essential circulating mediator of this protection is nitric oxide (NO) induced by lower limb RIPC. One of the mechanisms through which NO generally acts is the soluble guanylyl cyclase-cyclic GMP (sGC-cGMP) pathway. The present study aimed to assess the role of hepatic sGC-cGMP in lower limb RIPC-induced protection against liver IR injury.
Mice were allocated to 4 groups: 1.Sham; 2.IR: 40 min of lobar hepatic ischemia and 2 hr reperfusion; 3.RIPC+IR: 6 cycles of 4x4 min IR of the lower limb followed by IR group procedure; (4) 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ)+RIPC+IR: ODQ (sGC inhibitor) was administered followed by RIPC+IR group procedure. Hepatic microcirculatory blood flow (MBF) was measured throughout the experiment. Plasma transaminases, hepatic histopathological and transmission electron microscopy studies were performed at the end of the experiment. Hepatic cGMP levels were measured in groups 1-3 in addition to an RIPC alone group.
Compared to liver IR alone, RIPC+IR increased hepatic MBF during liver reperfusion (P<0.05), and reduced plasma transaminases (P<0.05) and ultrastructural markers of injury. In contrast compared to RIPC+IR, ODQ+RIPC+IR decreased hepatic MBF (P<0.05) and ultrastructural markers of injury. However, plasma transaminases were not significantly different in the ODQ+RIPC+IR compared to the RIPC+IR group. Hepatic cGMP levels were significantly elevated in the RIPC compared to sham group.
The hepatic sGC-cGMP pathway is required for mediating the protective effects of lower limb RIPC on hepatic MBF in liver IR injury.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>22456530</pmid><doi>10.1097/TP.0b013e31824cd59d</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Transplantation, 2012-05, Vol.93 (9), p.880-886 |
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| subjects | Animals Biological and medical sciences Cyclic GMP Cyclic GMP - metabolism Disease Models, Animal Follow-Up Studies Fundamental and applied biological sciences. Psychology Fundamental immunology Gastroenterology. Liver. Pancreas. Abdomen Guanosine Guanylate Cyclase - metabolism Injuries Ischemia Ischemic Preconditioning - methods Limbs Liver Liver - blood supply Liver - metabolism Liver - ultrastructure Liver Circulation - physiology Liver Diseases - metabolism Liver Diseases - physiopathology Liver Diseases - prevention & control Liver. Biliary tract. Portal circulation. Exocrine pancreas Medical sciences Mice Microcirculation - physiology Microscopy, Electron, Transmission Nitric oxide Other diseases. Semiology Receptors, Cytoplasmic and Nuclear - metabolism Reperfusion Reperfusion Injury - metabolism Reperfusion Injury - pathology Reperfusion Injury - prevention & control Soluble Guanylyl Cyclase Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Tissue, organ and graft immunology transaminase Transmission electron microscopy |
| title | The Hepatic Soluble Guanylyl Cyclase-Cyclic Guanosine Monophosphate Pathway Mediates the Protection of Remote Ischemic Preconditioning on the Microcirculation in Liver Ischemia-Reperfusion Injury |
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