An antidiabetic thiazolidinedione induces eccentric cardiac hypertrophy by cardiac volume overload in rats
An antidiabetic thiazolidinedione induces eccentric cardiac hypertrophy by cardiac volume overload in rats
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DOI：
10.1111/j.1440-1681.2004.03954.x
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发表时间：
2004-01-01
影响因子：
2.9
通讯作者：
Saito, A
中科院分区：
文献类型：
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作者：
Arakawa, K;Ishihara, T;Saito, A
1.为探讨容量超负荷在抗糖尿病药物噻唑烷二酮治疗大鼠心肌肥厚中的作用，观察了噻唑烷二酮衍生物T-174.2对雌性SD大鼠心脏解剖结构和心脏容量超负荷参数的影响。两周后给予T-174(每天13和114 mg/kg)，心脏绝对重量和相对重量增加11-24%，显示心肌肥厚的发展。治疗组大鼠心脏未见水肿的迹象。T-174处理的大鼠血浆和血容量均增加，但对收缩压和心率没有任何影响，而红细胞压积降低。随着容量超负荷的存在，左室舒张末压和右房压均升高。心脏形态计量学分析显示，T-174可引起心脏偏心性肥厚，其特征是室壁厚度略有增加，心腔容量明显增大，表现为容量超负荷。容量超负荷被认为是可能的触发机制，因为血容量膨胀先于心肌肥厚，且心脏重量与血容量高度相关。T-174治疗的链脲佐菌素诱导的糖尿病大鼠也表现出血容量扩张和心脏肥厚。这些发现提示，心脏容量超负荷是由血浆容量膨胀引起的，并在抗糖尿病药物治疗期间导致离心性心肌肥厚的发生。尽管噻唑烷二酮类药物是胰岛素增敏剂，但这些心脏效应很可能是独立于胰岛素介导的。
1. To assess the involvement of volume overload in the development of cardiac hypertrophy during treatment with an antidiabetic thiazolidinedione, changes in cardiac anatomy and parameters of cardiac volume overload were evaluated in female Sprague-Dawley rats treated with the thiazolidinedione derivative T-174.2. Two week administration of T-174 (13 and 114 mg/kg per day) increased absolute and relative heart weights by 11-24%, demonstrating the development of cardiac hypertrophy. There was no evidence of oedema in hearts from treated rats.3. Both plasma and blood volumes were increased in T-174-treated rats without any changes in systolic blood pressure and heart rate, whereas haematocrit was decreased. In accordance with the existence of volume overload, both left ventricular end-diastolic pressure and right atrial pressure were increased. Morphometric analysis of hearts revealed that T-174 induced eccentric heart hypertrophy, as characterized by a small increase in wall thickness and a large increase in the chamber volume, which is characteristic of volume overload. Volume overload is suggested as the possible trigger mechanism because blood volume expansion preceded cardiac hypertrophy and there was a high correlation between heart weight and blood volume.4. T-174-treated streptozotocin-induced diabetic rats also exhibited blood volume expansion and cardiac hypertrophy.5. These findings suggest that cardiac volume overload is induced by plasma volume expansion and contributes to the development of eccentric cardiac hypertrophy during treatment with antidiabetic thiazolidinediones. Although thiazolidinediones are insulin-sensitizing agents, these cardiac effects are likely to be mediated independently of insulin.