| Coronary microvascular dysfunction in a porcine model of early atherosclerosis and diabetes. | |
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MedLine Citation:
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PMID: 21984550 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Detailed evaluation of coronary function early in diabetes mellitus (DM)-associated coronary artery disease (CAD) development is difficult in patients. Therefore, we investigated coronary conduit and small artery function in a preatherosclerotic DM porcine model with type 2 characteristics. Streptozotocin-induced DM pigs on a saturated fat/cholesterol (SFC) diet (SFC + DM) were compared with control pigs on SFC and standard (control) diets. SFC + DM pigs showed DM-associated metabolic alterations and early atherosclerosis development in the aorta. Endothelium-dependent vasodilation to bradykinin (BK), with or without blockade of nitric oxide (NO) synthase, endothelium-independent vasodilation to an exogenous NO-donor (S-nitroso-N-acetylpenicillamine), and vasoconstriction to endothelin (ET)-1 with blockade of receptor subtypes, were assessed in vitro. Small coronary arteries, but not conduit vessels, showed functional alterations including impaired BK-induced vasodilatation due to loss of NO (P < 0.01 vs. SFC and control) and reduced vasoconstriction to ET-1 (P < 0.01 vs. SFC and control), due to a decreased ET(A) receptor dominance. Other vasomotor responses were unaltered. In conclusion, this model demonstrates specific coronary microvascular alterations with regard to NO and ET-1 systems in the process of early atherosclerosis in DM. In particular, the altered ET-1 system correlated with hyperglycemia in atherogenic conditions, emphasizing the importance of this system in DM-associated CAD development. |
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Authors:
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Mieke van den Heuvel; Oana Sorop; Sietse-Jan Koopmans; Ruud Dekker; René de Vries; Heleen M M van Beusekom; Etto C Eringa; Dirk J Duncker; A H Jan Danser; Willem J van der Giessen |
Publication Detail:
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Type: Journal Article Date: 2011-10-07 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 302 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2011-12-27 Completed Date: 2012-02-14 Revised Date: 2012-05-23 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H85-94 Citation Subset: IM |
Affiliation:
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Department of Cardiology, Division of Pharmacology, Vascular and Metabolic Diseases, Cardiovascular Research School COEUR, Erasmus University Medical Center, Rotterdam, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Glucose / metabolism Bradykinin / pharmacology Coronary Artery Disease / etiology*, metabolism, physiopathology Coronary Vessels / drug effects, metabolism, physiopathology* Diabetes Mellitus, Experimental / complications*, metabolism, physiopathology Diabetic Angiopathies / etiology*, metabolism, physiopathology Disease Progression Dose-Response Relationship, Drug Endothelin-1 / pharmacology Endothelium, Vascular / drug effects, metabolism, physiopathology* Male Nitric Oxide / metabolism Nitric Oxide Donors / pharmacology Receptors, Endothelin / drug effects, metabolism S-Nitroso-N-Acetylpenicillamine / pharmacology Swine Time Factors Vasoconstriction* / drug effects Vasoconstrictor Agents / pharmacology Vasodilation* / drug effects Vasodilator Agents / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Endothelin-1; 0/Nitric Oxide Donors; 0/Receptors, Endothelin; 0/Vasoconstrictor Agents; 0/Vasodilator Agents; 10102-43-9/Nitric Oxide; 58-82-2/Bradykinin; 79032-48-7/S-Nitroso-N-Acetylpenicillamine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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