| Role of cyclic guanosine monophosphate in late preconditioning in conscious rabbits. | |
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MedLine Citation:
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PMID: 12082001 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Although NO has been shown to serve both as the trigger and the mediator of the late phase of ischemic preconditioning (PC), it is unknown whether NO acts via activation of soluble guanylate cyclase (sGC). The objective of this study was to investigate the role of sGC in late PC in conscious rabbits using the selective sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). METHODS AND RESULTS: A total of 172 conscious rabbits were used. When nonpreconditioned rabbits were subjected to a sequence of 4-minute coronary occlusion/4-minute reperfusion cycles, myocardial cyclic guanosine monophosphate (cGMP) levels increased significantly at the end of the third and sixth occlusions. In rabbits preconditioned 24 hours earlier (on day 1) with six occlusion/reperfusion cycles, myocardial cGMP levels on day 2 were significantly higher than in nonpreconditioned rabbits even before ischemia but did not increase further during a second sequence of 4-minute occlusion/reperfusion cycles. Administration of ODQ before the six occlusion/reperfusion cycles on day 1 did not prevent the development of late PC against either stunning or infarction on day 2. In contrast, administration of ODQ on day 2 completely ablated the late PC effect against both stunning and infarction. CONCLUSIONS: These results indicate that enhanced synthesis of cGMP by sGC is not necessary for ischemia to trigger a late PC effect but is required for the protection to become manifest 24 hours later. This implies that NO participates in late PC via two distinct mechanisms; ie, it triggers late PC on day 1 via a cGMP-independent mechanism and it mediates late PC on day 2 via a cGMP-dependent mechanism. |
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Authors:
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Eitaro Kodani; Yu-Ting Xuan; Hitoshi Takano; Ken Shinmura; Xian-Liang Tang; Roberto Bolli |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Circulation Volume: 105 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2002 Jun |
Date Detail:
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Created Date: 2002-06-25 Completed Date: 2002-07-08 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: 3046-52 Citation Subset: AIM; IM |
Affiliation:
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Experimental Research Laboratory, Division of Cardiology, University of Louisville and the Jewish Heart and Lung Institute, Louisville, Ky 40292, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Consciousness Cyclic GMP / physiology* Enzyme Inhibitors / pharmacology Guanylate Cyclase / antagonists & inhibitors Ischemic Preconditioning, Myocardial* Kinetics Male Myocardial Infarction / enzymology, metabolism, prevention & control* Myocardial Stunning / enzymology, metabolism, prevention & control* Oxadiazoles / pharmacology Quinoxalines / pharmacology Rabbits |
| Grant Support | |
ID/Acronym/Agency:
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HL-55757/HL/NHLBI NIH HHS; HL-65660/HL/NHLBI NIH HHS; HL-68088/HL/NHLBI NIH HHS; R01 HL-43151/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; 0/Enzyme Inhibitors; 0/Oxadiazoles; 0/Quinoxalines; 7665-99-8/Cyclic GMP; EC 4.6.1.2/Guanylate Cyclase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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