| The ADP receptor P2Y(1) mediates t-PA release in pigs during cardiac ischemia. | |
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MedLine Citation:
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PMID: 17294140 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The endothelial ADP receptor P2Y(1) is responsible for a large part of the reactive hyperemia following cardiac ischemia. Tissue plasminogen activator (t-PA) increases during reactive hyperemia. We postulated that the release of t-PA during reactive hyperemia could be mitigated through blocking the coronary endothelial P2Y(1) receptor. METHODS: t-PA was measured in peripheral arterial blood and locally in the venous blood from the coronary sinus in a porcine model. The stable ADP analogue 2-MeSADP (10(-5) M), alone or as co-infusion with a selective P2Y(1) receptor blocker, MRS2179 (10(-3) M) was locally delivered in the left anterior descending artery through the tip of a coronary angioplasty balloon. In separate pigs the coronary artery was occluded with the balloon for 10 min. During the first and tenth minute of coronary ischemia, 2.5 ml of MRS2179 (10(-3) M) was delivered distal to the occlusion in 8 pigs, 10 pigs were used as controls. RESULTS: 2-MeSADP increased levels of t-PA in the coronary sinus, which could be significantly inhibited by co-infusion with MRS2179. During cardiac ischemia and reperfusion, t-PA increased significantly, an effect that could be significantly inhibited by MRS2179. CONCLUSIONS: Intra coronary administered MRS2179, a selective P2Y(1) receptor blocker, significantly reduces the increased levels of t-PA caused by both 2-MeSADP and cardiac ischemia in coronary arteries. Thus, ADP acting on the endothelial P2Y(1) receptor may mediate release of t-PA during ischemia and post-ischemic hyperemia, an effect that may counteract some of the platelet activating effects of ADP. Abbreviated Abstract We postulated that the release of t-PA during post ischemic reactive hyperemia could be mitigated through blocking the coronary endothelial P2Y(1) receptor in a porcine model. The ADP analogue 2-MeSADP (10(-5) M), alone or as co-infusion with a the P2Y(1) receptor blocker, MRS2179 (10(-3) M) was locally delivered in the left anterior descending artery. In separate pigs the coronary artery was occluded for ten min. During the first and tenth min of coronary ischemia, 2.5 ml of MRS2179 (10(-3) M) was delivered distal to the occlusion. t-PA was measured in peripheral arterial blood and also from the Coronary Sinus. We found that levels of t-PA in the blood from the coronary Sinus increased during infusion with 2-MeSADP as well as during ischemia and reperfusion. In pigs treated with MRS2179 levels of t-PA in the Coronary Sinus were significantly reduced during both coinfusion with 2-MeSADP and during ischemia/reperfusion. Thus, ADP acting on the endothelial P2Y(1) M receptor may mediate release of t-PA during ischemia and post-ischemic hyperemia, an effect that may counteract some of the platelet activating effects of ADP. |
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Authors:
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Goran K Olivecrona; Matthias Götberg; Jan Harnek; Kenneth A Jacobson; Sverker Jern; David Erlinge |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-02-10 |
Journal Detail:
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Title: Journal of thrombosis and thrombolysis Volume: 24 ISSN: 0929-5305 ISO Abbreviation: J. Thromb. Thrombolysis Publication Date: 2007 Oct |
Date Detail:
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Created Date: 2007-08-03 Completed Date: 2007-12-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9502018 Medline TA: J Thromb Thrombolysis Country: Netherlands |
Other Details:
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Languages: eng Pagination: 115-22 Citation Subset: IM |
Affiliation:
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Department of Cardiology, Lund University Hospital, Lund University, Lund 22185, Sweden. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Diphosphate
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analogs & derivatives,
pharmacology Angioplasty, Transluminal, Percutaneous Coronary Animals Hyperemia / etiology* Myocardial Ischemia / blood* Receptors, Purinergic P2 / antagonists & inhibitors, physiology* Swine Thionucleotides / pharmacology Tissue Plasminogen Activator / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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Z01 DK031116-20/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/2-methylthio-ADP; 0/N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; 0/Receptors, Purinergic P2; 0/Thionucleotides; 0/purinoceptor P2Y1; 58-64-0/Adenosine Diphosphate; EC 3.4.21.68/Tissue Plasminogen Activator |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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