Afzal N, Ganguly P K, Dhalla K S, Pierce G N, Singal P K, Dhalla N S
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Diabetes. 1988 Jul;37(7):936-42. doi: 10.2337/diab.37.7.936.
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.kg-1.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.kg-1.day-1) than with the lower doses (2 mg.kg-1.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.
有人提出，细胞内钙离子超载的发生可能导致糖尿病性心肌病的发展，这与高能磷酸储存的耗竭、超微结构紊乱和心脏功能障碍有关。因此，在通过静脉注射链脲佐菌素（65mg/kg）使大鼠患糖尿病的情况下，评估了钙离子拮抗剂维拉帕米对心肌心脏功能、超微结构和高能磷酸储存的影响。糖尿病诱导四周后，用三种剂量（2、4或8mg·kg-1·天-1）的维拉帕米对动物进行治疗，持续4周，直至用于测量不同参数。未经治疗的糖尿病动物心率较慢，收缩率和舒张率降低，左心室收缩压峰值较低，左心室舒张压升高。在接受维拉帕米治疗的糖尿病大鼠中，所有这些变化都得到了显著改善。维拉帕米的有益作用在高剂量（8mg·kg-1·天-1）时比低剂量（2mg·kg-1·天-1）时更明显。糖尿病动物还表现出心肌高能磷酸储存的改变，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。我们的结果表明，维拉帕米能够预防糖尿病引起的心肌变化，并支持钙离子在糖尿病期间心脏病理过程中的作用。
