Cannabinoid receptor 1 inhibition improves cardiac function and remodelling after myocardial infarction and in experimental metabolic syndrome.

Abstract

The cannabinoid receptors, CB1 and CB2, are expressed in the heart, but their role under pathological conditions remains controversial. This study examined the effect of CB1 receptor blockade on cardiovascular functions after experimental MI and in experimental metabolic syndrome. MI was induced in Wistar rats by permanent ligation of the left coronary artery. Treatment with the CB1 receptor antagonist rimonabant (10 mg/kg i.p. daily) started 7 days before or 6 h after MI and continued for 6 weeks. Haemodynamic parameters were measured via echocardiography and intracardiac Samba catheter. CB1 blockade improved systolic and diastolic heart function, decreased cardiac collagen and hydroxyproline content and down-regulated TGF-β1. Additionally, rimonabant decreased arterial stiffness, normalised QRS complex duration and reduced brain natriuretic peptide levels in serum. In primary cardiac fibroblasts, rimonabant decreased MMP-9 activity and TGF-β1 expression. Furthermore, rimonabant improved depressed systolic function of spontaneously hypertensive obese rats and reduced weight gain. Blocking of CB1 receptor with rimonabant improves cardiac functions in the early and late stages after MI, decreases arterial stiffness and reduces cardiac remodelling. Rimonabant also has cardioprotective actions in rats characterised by the metabolic syndrome. Inhibition of proteolysis and TGF-β1 expression and reduced collagen content by rimonabant may attenuate destruction of the extracellular matrix and decrease fibrosis after MI.

• Authors: Svetlana Slavic, Dilyara Lauer, Manuela Sommerfeld, Ulrich Rudolf Kemnitz, Aleksandra Grzesiak, Manuela Trappiel, Christa Thöne-Reineke, Johannes Baulmann, Ludovit Paulis, Kai Kappert, Ulrich Kintscher, Thomas Unger, Elena Kaschina
• Journal: Journal of molecular medicine (Berlin, Germany) (J Mol Med (Berl)) Vol. 91 Issue 7 Pg. 811-23 (Jul 2013) ISSN: 1432-1440 [Electronic] Germany
• PMID: 23636507 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cannabinoid Receptor Antagonists
• Cardiotonic Agents
• Piperidines
• Pyrazoles
• Receptor, Cannabinoid, CB1
• Transforming Growth Factor beta1
• Collagen
• Matrix Metalloproteinase 2
• Mmp2 protein, rat
• Matrix Metalloproteinase 9
• Mmp9 protein, rat
• Rimonabant

Topics

• Animals
• Cannabinoid Receptor Antagonists (pharmacology, therapeutic use)
• Cardiotonic Agents (pharmacology, therapeutic use)
• Cells, Cultured
• Collagen (metabolism)
• Fibroblasts (drug effects, metabolism)
• Heart (drug effects, physiology)
• Male
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Metabolic Syndrome (drug therapy, physiopathology)
• Myocardial Infarction (drug therapy, physiopathology)
• Piperidines (therapeutic use)
• Pyrazoles (therapeutic use)
• Rats
• Rats, Wistar
• Receptor, Cannabinoid, CB1 (antagonists & inhibitors)
• Rimonabant
• Transforming Growth Factor beta1 (metabolism)