[Role of cannabinoid receptors in regulation of cardiac tolerance to ischemia and reperfusion].

Abstract

Coronary artery occlusion (45 min) and reperfusion (2 h) were modeled in vivo in anesthetized artificially ventilated Wistar rats. Total ischemia (45 min) and reperfusion (30 min) of the isolated rat heart were performed in vitro. The selective agonist of cannabinoid (CB) receptors HU-210 was injected intravenously at a dose of 0.1 mg/kg 15 min prior to the coronary artery ligation. The selective CB1 antagonist SR141716A and the selective CB2 antagonist SR144528 were injected intravenously 25 min prior to ischemia. In vitro, HU-210 and SR141716A were added to the perfusion solution at the final concentrations of 0.1 microM prior to total ischemia. Preliminary injection of HU-210 reduced the infarct size-to-area at risk (IS/AAR) ratio in vivo. This cardioprotective effect was completely abolished by SR141716A but remained after SR144528 injection. Both antagonists had no effect on the IS/AAR ratio. Preliminary injection of the K(ATP) channel blocker glibenclamide did not abolish the cardioprotective effect of HU-210. The addition of HU-210 prior to ischemia reduced the creatine phosphokinase (CPK) level in the coronary effluent and decreased left ventricular developed pressure. SR141716A alone had no effect on cardiac contractility and CPK levels. These results suggest that cardiac CB1 receptor activation increases cardiac tolerance to ischemia-reperfusion and has a negative effect on the cardiac pump function. Endogenous cannabinoids are not involved in the regulation of cardiac contractility and tolerance to ischemia and reperfusion. ATP-sensitive E+ channels are not involved in the mechanism of the cardioprotective effect of HU-210.

• Authors: O V Lasukova, L N Maslov, S Iu Ermakov, D Crawford, F Barth, A V Krylatov, L O Hanus
• Journal: Izvestiia Akademii nauk. Seriia biologicheskaia (Izv Akad Nauk Ser Biol) 2008 Jul-Aug Issue 4 Pg. 471-8 ISSN: 1026-3470 [Print] Russia (Federation)
• PMID: 18771032 (Publication Type: Journal Article)

Chemical References

• Camphanes
• Cannabinoid Receptor Antagonists
• Piperidines
• Pyrazoles
• Receptors, Cannabinoid
• SR 144528
• Dronabinol
• Creatine Kinase
• HU 211
• Rimonabant

Topics

• Animals
• Camphanes (pharmacology, therapeutic use)
• Cannabinoid Receptor Antagonists
• Creatine Kinase (metabolism)
• Dronabinol (analogs & derivatives, pharmacology, therapeutic use)
• Heart Rate (drug effects, physiology)
• In Vitro Techniques
• Myocardial Contraction (drug effects, physiology)
• Myocardial Infarction (drug therapy, physiopathology)
• Myocardial Reperfusion Injury (drug therapy, physiopathology)
• Piperidines (pharmacology, therapeutic use)
• Pyrazoles (pharmacology, therapeutic use)
• Rats
• Rats, Wistar
• Receptors, Cannabinoid (metabolism)
• Rimonabant