Medical Plants Research Centre, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Basic Clin Pharmacol Toxicol. 2012 Aug;111(2):75-80. doi: 10.1111/j.1742-7843.2012.00860.x. Epub 2012 Feb 28.
Acute morphine administration decreases cardiac responses to ischaemic injury. This project has determined whether induction of morphine dependence in rats by gradually increasing morphine doses for 21 days induces structural and functional changes in the cardiovascular system because of mineralocorticoid receptor activation, as morphine increases plasma corticosterone concentrations. Morphine-dependent rats showed ventricular hypertrophy, increased collagen deposition in the left ventricle together with an increased ventricular stiffness and increased plasma malondialdehyde concentrations without changes in systolic blood pressure or thoracic aortic responsiveness. These parameters were attenuated or normalised in morphine-dependent rats treated with spironolactone (50 mg/kg/day) from days 14-21. These results suggest that morphine dependence induces ventricular remodelling and increased oxidative stress that can be prevented by the mineralocorticoid receptor antagonist, spironolactone.
急性吗啡给药可降低心脏对缺血损伤的反应。本项目通过在 21 天内逐渐增加吗啡剂量来确定是否在大鼠中诱导吗啡依赖，是否会由于盐皮质激素受体激活而导致心血管系统的结构和功能变化，因为吗啡会增加血浆皮质酮浓度。吗啡依赖大鼠表现出心室肥厚，左心室胶原沉积增加，心室僵硬度增加，血浆丙二醛浓度增加，但收缩压或胸主动脉反应性没有变化。在吗啡依赖大鼠中，从第 14 天到第 21 天每天给予螺内酯（50mg/kg）可减轻或使这些参数正常化。这些结果表明，吗啡依赖可诱导心室重构和增加氧化应激，而盐皮质激素受体拮抗剂螺内酯可预防这种情况。
