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Cannabinoid/agonist WIN 55,212-2 reduces cardiac ischaemia–reperfusion injury in Zucker diabetic fatty rats: role of CB2 receptors and iNOS/eNOS.

Abstract

BACKGROUND

Diabetes increases cardiac damage after myocardial ischaemia. Cannabinoids can protect against myocardial ischaemia/reperfusion injury. The aim of this study was to examine the cardioprotective effect of the cannabinoid agonist WIN 55,212-2 (WIN) against ischaemia/reperfusion injury in an experimental model of type 2 diabetes. We performed these experiments in the Zucker diabetic fatty rat, and focused on the role of cannabinoid receptors in modulation of cardiac inducible nitric oxide synthase (iNOS)/endothelial-type nitric oxide synthase (eNOS) expression.

METHODS

Male 20-week-old Zucker diabetic fatty 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 ischaemia/reperfusion injury was evaluated. In addition, cardiac iNOS and eNOS expression were determined by western blot.

RESULTS

WIN significantly improved cardiac recovery after ischaemia/ reperfusion in the hearts from Zucker diabetic fatty rats by restoring coronary perfusion pressure and heart rate to preischaemic levels. Additionally, WIN decreased cardiac iNOS expression and increased eNOS expression after ischaemia/reperfusion 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 CB antagonists.

CONCLUSIONS

This study shows a cardioprotective effect of a cannabinoid agonist on ischaemia/reperfusion injury in an experimental model of a metabolic disorder. The activation mainly of CB2 receptors and the restoration of iNOS/eNOS cardiac equilibrium are mechanisms involved in this protective effect. These initial studies have provided the basis for future research in this field.

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  • Authors+Show Affiliations

    ,

    Universidad Rey Juan Carlos, Facultad Ciencias de la Salud, Dpto. Farmacología y Nutrición, Alcorcón, Madrid, Spain.

    , , , , , ,

    Source

    MeSH

    Animals
    Benzoxazines
    Cannabinoids
    Cardiotonic Agents
    Coronary Vessels
    Diabetes Mellitus, Type 2
    Heart
    Heart Rate
    Indoles
    Male
    Morpholines
    Myocardial Ischemia
    Myocardial Reperfusion Injury
    Naphthalenes
    Nitric Oxide Synthase Type II
    Nitric Oxide Synthase Type III
    Piperidines
    Pyrazoles
    Rats
    Rats, Zucker
    Receptor, Cannabinoid, CB1
    Receptor, Cannabinoid, CB2

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21309057

    Citation

    González, Cristina, et al. "Cannabinoid/agonist WIN 55,212-2 Reduces Cardiac Ischaemia–reperfusion Injury in Zucker Diabetic Fatty Rats: Role of CB2 Receptors and INOS/eNOS." Diabetes/metabolism Research and Reviews, vol. 27, no. 4, 2011, pp. 331-40.
    González C, Herradón E, Abalo R, et al. Cannabinoid/agonist WIN 55,212-2 reduces cardiac ischaemia–reperfusion injury in Zucker diabetic fatty rats: role of CB2 receptors and iNOS/eNOS. Diabetes Metab Res Rev. 2011;27(4):331-40.
    González, C., Herradón, E., Abalo, R., Vera, G., Pérez-Nievas, B. G., Leza, J. C., ... López-Miranda, V. (2011). Cannabinoid/agonist WIN 55,212-2 reduces cardiac ischaemia–reperfusion injury in Zucker diabetic fatty rats: role of CB2 receptors and iNOS/eNOS. Diabetes/metabolism Research and Reviews, 27(4), pp. 331-40. doi:10.1002/dmrr.1176.
    González C, et al. Cannabinoid/agonist WIN 55,212-2 Reduces Cardiac Ischaemia–reperfusion Injury in Zucker Diabetic Fatty Rats: Role of CB2 Receptors and INOS/eNOS. Diabetes Metab Res Rev. 2011;27(4):331-40. PubMed PMID: 21309057.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Cannabinoid/agonist WIN 55,212-2 reduces cardiac ischaemia–reperfusion injury in Zucker diabetic fatty rats: role of CB2 receptors and iNOS/eNOS. AU - González,Cristina, AU - Herradón,Esperanza, AU - Abalo,Raquel, AU - Vera,Gema, AU - Pérez-Nievas,Beatriz G, AU - Leza,Juan Carlos, AU - Martín,Ma Isabel, AU - López-Miranda,Visitación, PY - 2011/2/11/entrez PY - 2011/2/11/pubmed PY - 2011/8/30/medline SP - 331 EP - 40 JF - Diabetes/metabolism research and reviews JO - Diabetes Metab. Res. Rev. VL - 27 IS - 4 N2 - BACKGROUND: Diabetes increases cardiac damage after myocardial ischaemia. Cannabinoids can protect against myocardial ischaemia/reperfusion injury. The aim of this study was to examine the cardioprotective effect of the cannabinoid agonist WIN 55,212-2 (WIN) against ischaemia/reperfusion injury in an experimental model of type 2 diabetes. We performed these experiments in the Zucker diabetic fatty rat, and focused on the role of cannabinoid receptors in modulation of cardiac inducible nitric oxide synthase (iNOS)/endothelial-type nitric oxide synthase (eNOS) expression. METHODS: Male 20-week-old Zucker diabetic fatty 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 ischaemia/reperfusion injury was evaluated. In addition, cardiac iNOS and eNOS expression were determined by western blot. RESULTS: WIN significantly improved cardiac recovery after ischaemia/ reperfusion in the hearts from Zucker diabetic fatty rats by restoring coronary perfusion pressure and heart rate to preischaemic levels. Additionally, WIN decreased cardiac iNOS expression and increased eNOS expression after ischaemia/reperfusion 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 CB antagonists. CONCLUSIONS: This study shows a cardioprotective effect of a cannabinoid agonist on ischaemia/reperfusion injury in an experimental model of a metabolic disorder. The activation mainly of CB2 receptors and the restoration of iNOS/eNOS cardiac equilibrium are mechanisms involved in this protective effect. These initial studies have provided the basis for future research in this field. SN - 1520-7560 UR - https://www.unboundmedicine.com/medline/citation/21309057/abstract/Win_55212_2_reduces_cardiac_ischaemia_reperfusion_injury_in_zucker_diabetic_fatty_rats:_role_of_cb2_receptors_and_cardiac_inos/enos_expression_ L2 - https://doi.org/10.1002/dmrr.1176 DB - PRIME DP - Unbound Medicine ER -