Dopamine mimics the cardioprotective effect of ischemic preconditioning via activation of alpha(1)-adrenoceptors in the isolated rat heart

The aim of the present study was to clarify whether pharmacological preconditioning with dopamine protects the heart against ischemia and whether this effect is mediated through dopaminergic receptors (D-1 and D-2) or alpha(1)-adrenoceptors. Isolated perfused rat hearts were either non-preconditioned, preconditioned with 5 min ischemia, or treated for 5 min with dopamine (1, 5 or 10 mu M) before being subjected to 45 min of sustained ischemia followed by 60 min reperfusion. Postischemic functional recovery and infarct size were used as indices of the effects of ischemia. Treatment with the lower concentration of dopamine (1 mu M), did not provide any protection to the ischemic myocardium. On the other hand, treatment with 5 mu M dopamine resulted in significantly improved functional recovery, whereas administration of dopamine (10 mu M) resulted in significantly improved functional recovery as well as reduction of infarct size. Pretreatment with the mixed D-1/D-2 dopaminergic receptor antagonist haloperidol or the P-adrenoceptor selective antagonist propranolol did not attenuate the protective effect of pharmacological preconditioning with 10 mu M dopamine with respect to both functional recovery and infarct size reduction. On the other hand, the cardioprotective effect of dopamine was blocked when the alpha(1)-adrenoceptor selective antagonist, prazosin, was administered. In conclusion, pharmacological preconditioning with dopamine protects the myocardium against ischemia and this effect seems to be mediated through activation of alpha(1)-adrenoceptors.