Activation of adenylate cyclase system in the preconditioned rat heart

Ischemic preconditioning (IP) protects the heart against subsequent prolong ed ischemia. Whether the beta-adrenoceptor/adenylate cyclase pathway contri butes to this cardioprotection is not yet fully known. Using enzyme catalyt ic cytochemistry we studied the adenylate cyclase activity and its distribu tion in the preconditioned rat heart. Adenylate cyclase activity was examin ed in Langendorff-perfuse rat hearts subjected to the following conditions: control perfusion; 30 min regional ischemia; 5 min occlusion and 10 min re perfusion (IP); IP followed by ischemia. Ischemia-induced arrhythmias and t he effect of ischemic preconditioning on the incidence of arrhythmias were analyzed. At the end of experiment the heart was shortly prefixed with glut araldehyde. Tissue samples from the left ventricle were incubated in a medi um containing the specific substrate AMP-PNP for adenylate cyclase and then routinely processed for electron microscopy. Adenylate cyclase activity wa s cytochemically demonstrated in the sarcolemma and the junctional sarcopla smic reticulum (JSR) in control hearts, while it was absent after test isch emia. The highest activity of the precipitate was observed after ischemic p reconditioning. In the preconditioned hearts followed by test ischemia, ade nylate cyclase activity in the precipitate was preserved in sarcolemma and even more in JSR. Protective effect of ischemic preconditioning was manifes ted by the suppression of severe arrhythmias. These results indicate the in volvement of the adenylate cyclase system in mechanisms underlying ischemic preconditioning.