We have previously shown that chronic treatment with propranolol had beneficial effects on heart function in rats during increasing-age in a gender-dependent manner. Herein, we hypothesize that propranolol would improve cardiac function in diabetic cardiomyopathy and investigated the benefits of chronic oral administration of propranolol on the parameters of Ca(2+) signaling in the heart of streptozotocin-diabetic rats. Male diabetic rats received propranolol (25 mg/kg, daily) for 12 weeks, 1 week after diabetes induction. Treatment of the diabetic rats with propranolol did not produce a hypoglycaemic effect whereas it attenuated the increased cell size. Basal and β-agonist response levels of left ventricular developed pressure were significantly higher in propranolol-treated diabetic rats relative to untreated diabetics while left ventricular end diastolic pressure of the treated diabetics was comparable to the controls. Propranolol treatment normalized also the prolongation of the action potential in papillary muscles from the diabetic rat hearts. This treatment attenuated the parameters of Ca(2+) transients, depressed Ca(2+) loading of the sarcoplasmic reticulum, and of the basal intracellular Ca(2+) level of diabetic cardiomyocytes. Furthermore, Western blot data indicated that the diabetes-induced alterations in the cardiac ryanodine receptor Ca(2+) release channel's hyperphosphorylation decreased the FKBP12.6 protein level. Also, the high phosphorylated levels of PKA and CaMKII were prevented with propranolol treatment. Chronic treatment with propranolol seems to prevent diabetes-related changes in heart function by controlling intracellular Ca(2+) signaling and preventing the development of left ventricular remodeling in diabetic cardiomyopathy.

中文翻译：

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心得安对糖尿病诱导的大鼠细胞内 Ca2+ 信号改变的心脏保护作用。

我们之前已经表明，心得安长期治疗对大鼠随年龄增长的心脏功能具有性别依赖性。在此，我们假设普萘洛尔会改善糖尿病心肌病的心脏功能，并研究了慢性口服普萘洛尔对链脲佐菌素-糖尿病大鼠心脏中 Ca(2+) 信号传导参数的益处。雄性糖尿病大鼠在糖尿病诱导后 1 周接受普萘洛尔（25 毫克/公斤，每天）治疗 12 周。用普萘洛尔治疗糖尿病大鼠不会产生降血糖作用，但会减弱增加的细胞大小。与未治疗的糖尿病大鼠相比，普萘洛尔治疗的糖尿病大鼠左心室发展压力的基础和β-激动剂反应水平显着更高，而治疗糖尿病患者的左心室舒张末期压力与对照组相当。普萘洛尔治疗也使糖尿病大鼠心脏乳头肌动作电位的延长正常化。这种治疗减弱了 Ca(2+) 瞬变的参数，抑制了肌浆网的 Ca(2+) 负载和糖尿病心肌细胞的基底细胞内 Ca(2+) 水平。此外，蛋白质印迹数据表明糖尿病引起的心脏兰尼碱受体 Ca(2+) 释放通道的过度磷酸化的改变降低了 FKBP12.6 蛋白水平。还，心得安治疗可防止 PKA 和 CaMKII 的高磷酸化水平。心得安的慢性治疗似乎通过控制细胞内 Ca(2+) 信号传导和防止糖尿病心肌病左心室重构的发展来防止与糖尿病相关的心脏功能变化。