1. [Mediated role of NO-syntase, protein kinase C and KATP-channels in realization of cardioprotective impact of cannabinoid HU-210].
- Author
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Maslov LN, Lasukova OV, Krylatov AV, Khanush L, and Lishmanov IuB
- Subjects
- Animals, Benzophenanthridines pharmacology, Dronabinol pharmacology, Glyburide pharmacology, Heart drug effects, Heart physiopathology, KATP Channels antagonists & inhibitors, Male, Myocardial Reperfusion Injury metabolism, Myocardial Reperfusion Injury physiopathology, NG-Nitroarginine Methyl Ester pharmacology, Nitric Oxide Synthase Type III antagonists & inhibitors, Organ Culture Techniques, Potassium Channel Blockers pharmacology, Protein Kinase C antagonists & inhibitors, Protein Kinase Inhibitors pharmacology, Rats, Rats, Wistar, Receptor, Cannabinoid, CB1 metabolism, Receptor, Cannabinoid, CB2 metabolism, Signal Transduction, Cannabinoid Receptor Agonists pharmacology, Cardiotonic Agents pharmacology, Dronabinol analogs & derivatives, KATP Channels metabolism, Myocardial Reperfusion Injury prevention & control, Nitric Oxide Synthase Type III metabolism, Protein Kinase C metabolism
- Abstract
It was shown that perfusion of the isolated heart of rat with solution containing the CB1- and CB2-receptor agonist HU-210 at concentrations of 0.1 or 1.0 microM/L for a duration of 10 min at 20 min before global ischemia (45 min) and reperfusion (30 min) promotes a twofold decrease in creatine kinase levels in coronary effluent. It was established that KATP channel blockade by glibenclamide (1 microM/L) or inhibition of protein kinase C (2 microM/L) by chelerythrine abolishes the cardioprotective effect of HU-210. The inhibitor of NO synthase L-NAME (1 microM/L) had no effect on the anti-necrotic effect of HU-210. Thus, the intracellular signaling mechanism of the cardioprotective effect of the CB-agonist HU-210 involves the activation of KATP channels and protein kinase C without the participation of NO-synthase.
- Published
- 2012