| Dipyridamole enhances ischaemia-induced arteriogenesis through an endocrine nitrite/nitric oxide-dependent pathway. | |
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MedLine Citation:
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PMID: 20061326 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS: Anti-platelet agents, such as dipyridamole, have several clinical benefits for peripheral artery disease with the speculation of angiogenic potential that could preserve ischaemic tissue viability, yet the effect of dipyridamole on ischaemic arteriogenesis or angiogenesis is unknown. Here we test the hypothesis that dipyridamole therapy augments arteriolar vessel development and function during chronic ischaemia. METHODS AND RESULTS: Mice were treated with 200 mg/kg dipyridamole twice daily to achieve therapeutic plasma levels (0.8-1.2 microg/mL). Chronic hindlimb ischaemia was induced by permanent femoral artery ligation followed by measurement of tissue perfusion using laser Doppler blood flow along with quantification of vascular density, cell proliferation, and activation of nitric oxide (NO) metabolism. Dipyridamole treatment quickly restored ischaemic hindlimb blood flow, increased vascular density and cell proliferation, and enhanced collateral artery perfusion compared with control treatments. The beneficial effects of dipyridamole on blood flow and vascular density were dependent on NO production as dipyridamole did not augment ischaemic tissue reperfusion, vascular density, or endothelial cell proliferation in endothelial NO synthase (eNOS)-deficient mice. Blood and tissue nitrite levels were significantly higher in dipyridamole-treated mice compared with controls and eNOS(-/-) mice, verifying increased NO production that was regulated in a PKA-dependent manner. CONCLUSION: Dipyridamole augments nitrite/NO production, leading to enhanced arteriogenesis activity and blood perfusion in ischaemic limbs. Together, these data suggest that dipyridamole can augment ischaemic vessel function and restore blood flow, which may be beneficial in peripheral artery disease. |
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Authors:
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Prasanna K Venkatesh; Christopher B Pattillo; Billy Branch; Jay Hood; Steven Thoma; Sandra Illum; Sibile Pardue; Xinjun Teng; Rakesh P Patel; Christopher G Kevil |
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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: 2010-01-08 |
Journal Detail:
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Title: Cardiovascular research Volume: 85 ISSN: 1755-3245 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-02-11 Completed Date: 2010-04-26 Revised Date: 2011-07-25 |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: England |
Other Details:
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Languages: eng Pagination: 661-70 Citation Subset: IM |
Affiliation:
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Department of Cardiology, LSUHSC-Shreveport, Shreveport, LA 71130, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Division / drug effects, physiology Chronic Disease Cyclic AMP-Dependent Protein Kinases / metabolism Dipyridamole / blood, pharmacology* Dose-Response Relationship, Drug Enzyme Activation / drug effects Hindlimb / blood supply Ischemia / drug therapy*, metabolism, physiopathology Laser-Doppler Flowmetry Mice Mice, Inbred C57BL Mice, Mutant Strains Neovascularization, Physiologic / drug effects*, physiology Nitric Oxide / metabolism Nitric Oxide Synthase Type III / genetics, metabolism* Nitrites / metabolism Peripheral Vascular Diseases / drug therapy, metabolism, physiopathology Platelet Aggregation Inhibitors / blood, pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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HL80482/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Nitrites; 0/Platelet Aggregation Inhibitors; 10102-43-9/Nitric Oxide; 58-32-2/Dipyridamole; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, mouse; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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