The involvement of central beta-endorphin in the cardioprotective effects of remote preconditioning mediated by the intracerebroventricular administration of morphine.

Abstract

Opioids can mimic the effects of remote cardiac preconditioning and mediate a subsequent reduction in myocardial infarct size. This study investigated the role of beta-endorphin (β-EP) in intracerebroventricular morphine cardioprotection. Anesthetized, open-chest, male Sprague-Dawley rats were assigned to 1 of 9 treatment groups 3days after intracerebroventricular catheter placement. Remote preconditioning was induced with 3μg/kg of morphine. The β-EP antagonist was administered via intracerebroventricular or intravenous routes either 10min before or immediately after morphine or saline administration. Ischemia-reperfusion injury was caused by 30min of left coronary artery occlusion followed by 120min of reperfusion. The infarct size, as a percentage of the area at risk, was determined by 2,3,5-triphenyltetrazolium staining. Radioimmunoassay and immunoreactivity were used to determine the β-EP levels in the serum and brain. Intracerebroventricular administration of β-EP antiserum (AEP) after morphine administration attenuated the cardioprotective effects of remote preconditioning. The addition of intravenous AEP either before or after morphine did not affect infarct size. After morphine preconditioning, the β-EP level decreased in the hypothalamic arcuate nucleus and increased significantly in the serum, pituitary gland, ventrolateral periaqueductal gray and rostral ventrolateral medulla. Central but not peripheral β-EP is involved in morphine remote preconditioning and plays a role in the ongoing mediation of cardioprotective effects.