Document Detail


Impaired coronary function in Wistar Ottawa Karlsburg W rats-a new model of the metabolic syndrome.
MedLine Citation:
PMID:  17473932     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The metabolic syndrome is associated with an increased risk for coronary heart disease. The underlying mechanisms are not well understood. The present study was designed to investigate coronary function in Wistar Ottawa Karlsburg W (WOKW) rats, a new animal model of the metabolic syndrome. The responses of coronary artery segments from WOKW and Dark Agouti (DA) control rats of different ages to several physiological vasoconstrictors and vasodilators were measured in a small vessel wire myograph, and potential mechanisms involved in the differential responses between the two strains were investigated. WOKW showed increased alpha(1)-adrenoceptor-mediated coronary constriction at 3 and 10 months of age, as well as seriously blunted beta-adrenoceptor-mediated coronary relaxation at 16 months of age. Responses to non-adrenergic agonists were not altered in WOKW compared to DA. The alpha(1)-adrenoceptor-mediated coronary constriction in WOKW was completely blocked by rho-kinase inhibition. Induced hyperinsulinemia did not cause increased alpha(1)-adrenoceptor-mediated coronary constriction or impaired beta-adrenoceptor-mediated coronary relaxation in DA. The association between blunted coronary beta-adrenoceptor responsiveness and the metabolic syndrome was confirmed in Zucker diabetic fatty rats. We conclude that the metabolic syndrome in WOKW rats is associated with impaired coronary function due to altered adrenoceptor sensitivity. The latter may contribute to inappropriately elevated coronary tone in insulin-resistant subjects, especially when sympathetic activity to the heart is increased.
Authors:
Olaf Grisk; Tillmann Frauendorf; Torsten Schlüter; Ingrid Klöting; Beate Kuttler; Alexander Krebs; Jan Lüdemann; Rainer Rettig
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-05-01
Journal Detail:
Title:  Pflügers Archiv : European journal of physiology     Volume:  454     ISSN:  0031-6768     ISO Abbreviation:  Pflugers Arch.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-08-29     Completed Date:  2008-01-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0154720     Medline TA:  Pflugers Arch     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1011-21     Citation Subset:  IM    
Affiliation:
Department of Cardiovascular Medicine, Institute of Physiology, University of Greifswald, Greifswalder Str. 11c, 17495, Karlsburg, Germany. grisko@uni-greifswald.de
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MeSH Terms
Descriptor/Qualifier:
Aging / physiology
Animals
Blood Pressure / physiology
Calcium / metabolism
Coronary Vessels / physiopathology*
Creatinine / metabolism
Disease Models, Animal
Drug Implants
Extracellular Space / metabolism
Hyperinsulinism / metabolism
Hypoglycemic Agents / administration & dosage,  pharmacology
Insulin / administration & dosage,  pharmacology
Male
Metabolic Syndrome X / physiopathology*
Muscle, Smooth, Vascular / physiology
Myography
Norepinephrine / physiology
Proteinuria / genetics,  metabolism
Rats
Rats, Inbred Strains
Rats, Zucker
Receptors, Adrenergic, alpha-1 / physiology
Receptors, Adrenergic, alpha-2 / physiology
Vasoconstriction / physiology
Vasodilation / physiology
rhoA GTP-Binding Protein / metabolism
Chemical
Reg. No./Substance:
0/Drug Implants; 0/Hypoglycemic Agents; 0/Receptors, Adrenergic, alpha-1; 0/Receptors, Adrenergic, alpha-2; 11061-68-0/Insulin; 51-41-2/Norepinephrine; 60-27-5/Creatinine; 7440-70-2/Calcium; EC 3.6.5.2/rhoA GTP-Binding Protein

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