Title screen

The objectives of this study were to investigate the role of endogenous opioids in the mediation of stress-induced cardiomyopathy (SIC), and to evaluate which opioid receptors regulate heart resistance to immobilization stress. Wistar rats were subjected to 24 h immobilization stress. Stress-induced heart injury was assessed by 99mTc-pyrophosphate accumulation in the heart. The opioid receptor (OR) antagonists (naltrexone, NxMB - naltrexone methyl bromide, MR 2266, ICI 174.864) and agonists (DALDA, DAMGO, DSLET, U-50,488) were administered intraperitoneally prior to immobilization and 12 h after the start of stress. In addition, the selective µ OR agonists PL017 and DAMGO were administered intracerebroventricularly prior to stress. Finally pretreatment with guanethidine was used. Naltrexone did not alter the cardiac 99mTc-PP accumulation in stressed rats. NxMB aggravated stress-induced cardiomyopathy (P=0.005) (SIC). The selective µ OR agonist DALDA, which does not cross the blood-brain barrier, completely prevented (P=0.006) SIC. The µ OR agonist DAMGO exhibited weaker effect than DALDA. The selective δ ligand (DSLET) and κ OR ligand (U-50,488) did not alter stress-induced 99mTc-pyrophosphate accumulation in the heart. Intracerebroventricular administration of the µ OR agonists aggravated SIC. Pretreatment with guanethidine abolished this effect (P=0.01). Guanethidine alone exhibited cardioprotective properties. A stimulation of central µ OR promotes an appearance of SIC. In contrast, stimulation of peripheral µ OR contributes to an increase in cardiac tolerance to stress.