Dopamine mimics the cardioprotective effect of ischemic preconditioning via activation of alpha1-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 (D1 and D2) or alpha1-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 microM) 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 microM), did not provide any protection to the ischemic myocardium. On the other hand, treatment with 5 microM dopamine resulted in significantly improved functional recovery, whereas administration of dopamine (10 microM) resulted in significantly improved functional recovery as well as reduction of infarct size. Pretreatment with the mixed D1/D2 dopaminergic receptor antagonist haloperidol or the beta-adrenoceptor selective antagonist propranolol did not attenuate the protective effect of pharmacological preconditioning with 10 microM dopamine with respect to both functional recovery and infarct size reduction. On the other hand, the cardioprotective effect of dopamine was blocked when the alpha1-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 alpha1-adrenoceptors.
Lazou
A
A
Laboratory of Animal Physiology, Dept. of Zoology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece. lazou@bio.auth.gr
Markou
T
T
Zioga
M
M
Vasara
E
E
Efstathiou
A
A
Gaitanaki
C
C
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D023421:Models, Animal; D009203:Myocardial Infarction / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D002316:Cardiotonic Agents; D018340:Receptors, Adrenergic, alpha-1; D004298:Dopamine