Role of cyclic nucleotides and NO synthase in mechanisms of cardioprotective effects of cannabinoid HU-210.

Isolated perfused rat heart was subjected to global ischemia (45 min) followed by reperfusion (30 min). Under these conditions, the level of creatine phosphokinase in the perfusate increased by 4.5 times. Perfusion (10 min) of the isolated heart with a solution containing cannabinoid HU-210 (0.1 or 1.0 μmol/liter) was followed by a 2-fold decrease in creatine phosphokinase level in the perfusate. The cardioprotective effect of HU-210 remained unchanged under condition of NO synthase inhibition. Cannabinoid HU-210 reduced the concentration of cAMP in the myocardium by 2 times during reperfusion, but did not affect it before and during ischemia. This agent also did not change the level of cGMP in the myocardium before and during ischemia and during reperfusion. The results of the experiment suggest that the cardioprotective effect of HU-210 can be determined by a decrease in cAMP level in the myocardium during reperfusion. cGMP and NO synthase do not contribute to cytoprotective effect of HU-210.