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Win 55,212-2 reduces cardiac ischaemia-reperfusion injury in zucker diabetic fatty rats: role of cb2 receptors and cardiac inos/enos expression.
MedLine Citation:
PMID:  21309057     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Diabetes increases cardiac damage after myocardial ischaemia. Cannabinoids can protect against myocardial ischaemia/reperfusion (IR) injury. The aim of this study was to examine the cardioprotective effect of the cannabinoid agonist WIN 55,212-2 (WIN) against IR in situations of type 2 diabetes. We performed these experiments in the Zucker Diabetic Fatty (ZDF) rat, an experimental model of type 2 diabetes, and we focused on the role of cannabinoid receptors and in cardiac iNOS/eNOS expression modulation. METHODS: Male 20-week-old ZDF rats were treated with vehicle, WIN, the selective CB1 or CB2 receptor antagonists AM251 and AM630, respectively, AM251 + WIN or AM630 + WIN. Hearts were isolated from these rats, and the cardiac functional response to IR injury was evaluated. In addition, cardiac iNOS and eNOS expression were determined by western blot. RESULTS: WIN significantly improved cardiac recovery after IR in hearts from ZDF rats by restoring coronary perfusion pressure and heart rate to preischaemic levels. Additionally, WIN decreased cardiac iNOS expression and increased eNOS expression after IR in diabetic hearts. WIN-induced cardiac functional recovery was completely blocked by the CB2 antagonist AM630. However, changes in NOS isoenzyme expression were not affected by the cannabinoid antagonists. CONCLUSIONS: This is the first study that shows a cardioprotective effect of a cannabinoid agonist on IR injury in an experimental model of metabolic disorder. The activation of, mainly, CB2 cannabinoid receptors and the restoration of iNOS/eNOS cardiac equilibrium were mechanisms involved in this protective effect. These initial studies have provided the basis for future research on this field. Copyright © 2011 John Wiley & Sons, Ltd.
Authors:
Cristina González; Esperanza Herradón; Raquel Abalo; Gema Vera; Beatriz G Pérez-Nievas; Juan Carlos Leza; Ma Isabel Martín; Visitación López-Miranda
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-1-25
Journal Detail:
Title:  Diabetes/metabolism research and reviews     Volume:  -     ISSN:  1520-7560     ISO Abbreviation:  -     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-2-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100883450     Medline TA:  Diabetes Metab Res Rev     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 John Wiley & Sons, Ltd.
Affiliation:
Universidad Rey Juan Carlos, Facultad Ciencias de la Salud, Dpto. Farmacología y Nutrición. Avda. Atenas s/n 28922 Alcorcón, Madrid.
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