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
In vitro binding of specific opioid ligands to their respective sites in membrane fractions and the contribution of individual receptor classes (mu, delta, kappa) was studied in rats after longlasting (up to 22 months) section of spinal dorsal roots at the cervical (C5.8) or thoracic (Th^) level. This procedure leads to autotomy or scratching of the skin on the operated side. The total number of receptors in the cervical and thoracic spinal cord was more than doubled in both operated and contralalteral part of the cord in comparison with intact controls of the same age. In the cervical region, this increase mainly represented a rise in the number of free receptors, whilst in the thoracic region both free and saturated receptors were increased. On the deafferented side, receptor selectivity, especially in the delta and kappa types was decreased.