McLaughlin P J
Department of Neuroscience and Anatomy, Pennsylvania State University, M.S. Hershey Medical Center, Hershey, PA 17033.
Life Sci. 1994;54(19):1423-31. doi: 10.1016/0024-3205(94)00597-4.
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.
已知内源性阿片类物质可调节神经和非神经系统的形态发生。本研究探讨内源性阿片类物质是否影响心脏发育。对1日龄大鼠急性给予纳曲酮（一种强效阿片类拮抗剂，可阻断阿片肽与阿片受体的相互作用），剂量为50 mg/kg。通过[3H]-胸腺嘧啶核苷掺入和放射自显影法测定，心室和心房中合成DNA的心肌细胞和心外膜细胞数量较对照水平显著增加。单次注射纳曲酮后，标记指数至少在12小时内显著升高。对从出生起就接触纳曲酮的10日龄大鼠进行检查发现，其标记指数更高，体重、心脏重量以及整个心脏和心室的面积测量值均增加。纳曲酮的作用并非通过交感神经系统或甲状腺激素介导。这些结果表明，一种阿片肽在心脏形成过程中起负性调节因子的作用。生命早期内源性阿片系统的改变可能导致心脏畸形发生。此外，这些数据表明阿片类拮抗剂对于心脏畸形可能具有重要的治疗作用。
