Document Detail

Coronary microvascular dysfunction in a porcine model of early atherosclerosis and diabetes.
MedLine Citation:
PMID:  21984550     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article     Date:  2011-10-07
Journal Detail:
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:
Created Date:  2011-12-27     Completed Date:  2012-02-14     Revised Date:  2012-05-23    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H85-94     Citation Subset:  IM    
Department of Cardiology, Division of Pharmacology, Vascular and Metabolic Diseases, Cardiovascular Research School COEUR, Erasmus University Medical Center, Rotterdam, The Netherlands.
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MeSH Terms
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*
Nitric Oxide / metabolism
Nitric Oxide Donors / pharmacology
Receptors, Endothelin / drug effects,  metabolism
S-Nitroso-N-Acetylpenicillamine / pharmacology
Time Factors
Vasoconstriction* / drug effects
Vasoconstrictor Agents / pharmacology
Vasodilation* / drug effects
Vasodilator Agents / pharmacology
Reg. No./Substance:
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

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