Opioid antagonist modulation of rat heart development

Endogenous opioids are known to regulate morphogenesis in both neural and non-neural systems. This study examined whether endogenous opioids influence cardiac development. Naltrexone, a potent opioid antagonist that blocks the interaction of opioid peptides and opioid receptors, was administered acutely (50 mg/kg) to 1-day old rats. The numbers of myocardial and epicardial cells in the ventricles and atria that synthesized DNA, as determined by [3H]-thymidine incorporation and autoradiography, were markedly increased from control levels. Labeling indices were significantly elevated for at least 12 hr following a single injection of naltrexone. Examination of 10-day old rats exposed to naltrexone from birth revealed higher labeling indices, as well as increases in body and heart weights and in areal measurements of the entire heart and the ventricles. The effects of naltrexone were not mediated through the sympathetic nervous system or thyroid hormone. These results lead one to suggest that an opioid peptide is tonically acting as a negative regulatory factor in the formation of the heart. Alterations in the endogenous opioid system in early life may contribute to cardiac dysmorphogenesis. Moreover, these data indicate that opioid antagonists could act as an important therapeutic influence with regard to cardiac malformations.