| Adenosine receptor regulation of coronary blood flow in Ossabaw miniature swine. | |
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MedLine Citation:
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PMID: 20855445 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Adenosine clearly regulates coronary blood flow (CBF); however, contributions of specific adenosine receptor (AR) subtypes (A(1), A(2A), A(2B), A(3)) to CBF in swine have not been determined. ARs generally decrease (A(1), A(3)) or increase (A(2A), A(2B)) cyclic adenosine monophosphate, a major mediator of vasodilation. We hypothesized that A(1) antagonism potentiates coronary vasodilation and coronary stent deployment in dyslipidemic Ossabaw swine elicits impaired vasodilation to adenosine that is associated with increased A(1)/A(2A) expression. The left main coronary artery was accessed with a guiding catheter allowing intracoronary infusions. After placement of a flow wire into the left circumflex coronary artery the responses to bolus infusions of adenosine were obtained. Steady-state infusion of AR-specific agents was achieved by using a small catheter fed over the flow wire in control pigs. CBF was increased by the A(2)-nonselective agonist 2-phenylaminoadenosine (CV1808) in a dose-dependent manner. Baseline CBF was increased by the highly A(1)-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), but not changed by other AR-specific agents. The nonselective A(2) antagonist 3,7-dimethyl-1-propargylxanthine and A(2A)-selective antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM241385) abolished adenosine-induced CBF, whereas A(2B) and A(3) antagonism had no effect. Dyslipidemia and stenting decreased adenosine-induced CBF ∼70%, whereas A(1), A(2A), and A(2B) mRNA were up-regulated in dyslipidemic versus control >5-fold and there was no change in the ratio of A(1)/A(2A) protein in microvessels distal to the stent. In control Ossabaw swine A(1) antagonism by DPCPX positively regulated basal CBF. Impaired adenosine-induced CBF after stenting in dyslipidemia is most likely caused by the altered balance between A(1) and A(2A) signaling, not receptor expression. |
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Authors:
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Xin Long; Eric A Mokelke; Zachary P Neeb; Mouhamad Alloosh; Jason M Edwards; Michael Sturek |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-09-20 |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 335 ISSN: 1521-0103 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-18 Completed Date: 2011-02-03 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: United States |
Other Details:
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Languages: eng Pagination: 781-7 Citation Subset: IM |
Affiliation:
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Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana 46202-5120, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine
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pharmacology Adenosine A2 Receptor Agonists / administration & dosage, pharmacology Adenosine A2 Receptor Antagonists / administration & dosage, pharmacology Animals Cholesterol / blood Coronary Circulation / drug effects, physiology* Dietary Fats / pharmacology Gene Expression / genetics Hemodynamics / physiology Hyperlipidemias / blood, chemically induced, metabolism, physiopathology Lipoproteins / blood Male Microvessels / metabolism Receptor, Adenosine A1 / physiology Receptor, Adenosine A2A / physiology Receptor, Adenosine A2B / physiology Receptor, Adenosine A3 / physiology Receptors, Purinergic P1 / physiology* Stents / adverse effects Swine Swine, Miniature / physiology* Triglycerides / blood Up-Regulation / genetics |
| Grant Support | |
ID/Acronym/Agency:
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HL062552/HL/NHLBI NIH HHS; RR013223/RR/NCRR NIH HHS; UL1-RR025761/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adenosine A2 Receptor Agonists; 0/Adenosine A2 Receptor Antagonists; 0/Dietary Fats; 0/Lipoproteins; 0/Receptor, Adenosine A1; 0/Receptor, Adenosine A2A; 0/Receptor, Adenosine A2B; 0/Receptor, Adenosine A3; 0/Receptors, Purinergic P1; 0/Triglycerides; 57-88-5/Cholesterol; 58-61-7/Adenosine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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