BENEFICIAL-EFFECTS OF VERAPAMIL IN DIABETIC CARDIOMYOPATHY
BENEFICIAL-EFFECTS OF VERAPAMIL IN DIABETIC CARDIOMYOPATHY
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DOI：
10.2337/diabetes.37.7.936
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发表时间：
1988-07-01
期刊：
影响因子：
7.7
通讯作者：
DHALLA, NS
中科院分区：
文献类型：
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作者：
AFZAL, N;GANGULY, PK;DHALLA, NS
已有研究表明，细胞内钙超载的发生可能导致糖尿病性心肌病的发展，这与高能磷酸盐储备的消耗和超微结构的紊乱和心功能障碍有关。因此，在静脉注射链脲佐菌素（65 mg/kg）制成糖尿病的大鼠中，评价了钙拮抗剂维拉帕米对心脏功能、超微结构和心肌中高能磷酸盐储存的影响。诱导糖尿病后四周，用三个剂量（2、4或8 mg. kg-1. d-1），持续4 wk，直至测定各项指标。未治疗的糖尿病动物心率减慢，收缩率和舒张率降低，左心室收缩压峰值降低，左心室舒张压升高。所有这些变化在接受维拉帕米治疗的糖尿病大鼠中均得到显著改善。维拉帕米的有益效果在较高剂量（8 mg. kg-1.第-1天）比用较低剂量（2 mg. kg-1.第-1天）。糖尿病动物还表现出心肌高能磷酸盐储备的改变，并表现出超微结构损伤的证据;这些异常通过维拉帕米治疗得到改善，而不影响其高血糖状态。我们的研究结果表明，维拉帕米是能够防止糖尿病引起的心肌变化，并支持在糖尿病期间的心脏病理的Ca 2+参与。
It has been suggested that the occurrence of an intracellular Ca2+ overload may result in the development of diabetic cardiomyopathy, which is associated with depletion of high-energy phosphate stores and a derangement of ultrastructure and cardiac dysfunction. Accordingly, the effects of verapamil, a Ca2+ antagonist, on cardiac function, ultrastructure, and high-energy phosphate stores in the myocardium were evaluated in rats made diabetic by an intravenous injection of streptozocin (65 mg/kg). Four weeks after the induction of diabetes, the animals were treated with three doses (2, 4, or 8 mg .cntdot. kg-1 .cntdot. day-1) of verapamil for 4 wk until they were used for the measurement of different parameters. Untreated diabetic animals had slower heart rates, depressed rate of contraction and rate of relaxation, lower peak left ventricular systolic pressure, and elevated left ventricular diastolic pressure. All of these changes were significantly improved in diabetic rats receiving verapamil treatment. The beneficial effects of verapamil were more evident with higher doses (8 mg .cntdot. kg-1 .cntdot. day-1) than with the lower doses (2 mg .cntdot. kg-1 .cntdot. day-1). The diabetic animals also showed alterations in myocardial high-energy phosphate stores and exhibited evidence of ultrastructural damage; these abnormalities were improved by verapamil treatment without affecting their hyperglycemic status. Our results demonstrate that verapamil is capable of preventing diabetes-induced myocardial changes and support the involvement of Ca2+ in the cardiac pathology during diabetes.