Document Detail

Inducible nitric oxide synthase depresses cardiac contractile function in Zucker diabetic fatty rats.
MedLine Citation:
PMID:  17976576     Owner:  NLM     Status:  MEDLINE    
Cardiac contractile dysfunction is a common occurrence in type 2 diabetes. The aim was to examine if inducible nitric oxide synthase (iNOS) causes cardiac dysfunction in Zucker diabetic fatty (ZDF) rats, a model of type 2 diabetes. ZDF and Zucker lean control rats (20 week old) were studied at 6 h after recovery from halothane anaesthesia and surgery that involved insertions of catheters into the iliac arteries, iliac veins and the left ventricle via the right carotid artery. Protein expression and activity of iNOS in the hearts were measured by immunostaining and arginine-citrulline conversion assay, respectively. Both groups had similar baseline left ventricular developed pressure and maximum rate of rise of left ventricular pressure (+dP/dt), but heart rate and rate pressure product were lower in the ZDF than control rats. Dobutamine dose-dependently increased left ventricular developed pressure, +dP/dt, heart rate and rate pressure product in both groups, but the responses were less in the diabetic than control rats. The activity and protein expression of iNOS and nitrotyrosine were higher in the hearts of the diabetic than control rats. Selective inhibition of iNOS by 1400 W (N-3-aminomethyl-benzyl-acetamidine) did not alter responses to dobutamine in the control rats, but augmented the effects of dobutamine on left ventricular developed pressure and rate pressure product in the diabetic rats. The results indicate that activation of iNOS contributed to left ventricular contractile dysfunction in the ZDF rats, and this was partially reversed by selective inhibition of the activity of iNOS.
Dongzhe Song; Kuo-Hsing Kuo; Reina Yao; Simon R Hutchings; Catherine C Y Pang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-10-12
Journal Detail:
Title:  European journal of pharmacology     Volume:  579     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-08     Completed Date:  2008-04-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  253-9     Citation Subset:  IM    
Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, 2176 Health Sciences Mall, Vancouver, B.C., Canada V6T 1Z3.
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MeSH Terms
Adrenergic beta-Agonists / administration & dosage,  pharmacology
Diabetes Mellitus, Type 2 / complications*,  physiopathology
Disease Models, Animal
Dobutamine / administration & dosage,  pharmacology
Dose-Response Relationship, Drug
Gene Expression Regulation, Enzymologic
Myocardial Contraction / physiology*
Nitric Oxide Synthase Type II / metabolism*
Rats, Zucker
Ventricular Function, Left / physiology*
Reg. No./Substance:
0/Adrenergic beta-Agonists; 34368-04-2/Dobutamine; EC Oxide Synthase Type II

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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