Bhadada Shraddha V, Goyal Ramesh K
Department of Pharmacology, L.M. College of Pharmacy, Ahmedabad - 380 009, Gujarat, India.
Can J Physiol Pharmacol. 2007 Aug;85(8):831-6. doi: 10.1139/y07-069.
Recently, various clinical studies have indicated that lipophilic beta-blockers reduce the coronary mortality in diabetic patients; however, systematic studies have not been reported. The objective of the present investigation was to compare the effects of chronic treatment with metoprolol and atenolol on cardiovascular complications in streptozotocin (STZ)-induced diabetic rats. Injection of STZ produced hyperglycemia, hypoinsulinemia, hyperlipidemia, increased blood pressure, cardiac hypertrophy, reduction in heart rate, and structural alterations in cardiac tissues. Metoprolol and atenolol effectively prevented the development of hypertension in diabetic rats. Metoprolol treatment produced a slight but significant reduction in serum glucose levels with elevation in serum insulin levels, while atenolol produced a slight increase in glucose levels but no effect on insulin levels. Moreover, neither metoprolol nor atenolol treatment reduced the elevated cholesterol levels in diabetic rats. Metoprolol treatment significantly prevented STZ-induced increase in triglyceride levels, but atenolol failed to produce this effect. Metoprolol exhibited a minimal improvement in STZ-induced bradycardia, whereas atenolol produced a further reduction in heart rate. Histological examination showed metoprolol treatment also prevented STZ-induced hypertrophy and some of the alterations in cardiomyocytes. In conclusion, our data suggest that metoprolol has some beneficial effects over atenolol with respect to cardiovascular complications associated with diabetes mellitus.
最近,多项临床研究表明,亲脂性β受体阻滞剂可降低糖尿病患者的冠状动脉死亡率;然而,尚未见系统性研究报道。本研究的目的是比较美托洛尔和阿替洛尔长期治疗对链脲佐菌素(STZ)诱导的糖尿病大鼠心血管并发症的影响。注射STZ导致糖尿病大鼠出现高血糖、低胰岛素血症、高脂血症、血压升高、心脏肥大、心率降低以及心脏组织结构改变。美托洛尔和阿替洛尔有效预防了糖尿病大鼠高血压的发展。美托洛尔治疗使血清葡萄糖水平略有但显著降低,同时血清胰岛素水平升高,而阿替洛尔使葡萄糖水平略有升高,但对胰岛素水平无影响。此外,美托洛尔和阿替洛尔治疗均未降低糖尿病大鼠升高的胆固醇水平。美托洛尔治疗显著预防了STZ诱导的甘油三酯水平升高,但阿替洛尔未能产生此效果。美托洛尔对STZ诱导的心动过缓有轻微改善,而阿替洛尔使心率进一步降低。组织学检查显示,美托洛尔治疗还预防了STZ诱导的心肌肥大和心肌细胞的一些改变。总之,我们的数据表明,在与糖尿病相关的心血管并发症方面,美托洛尔比阿替洛尔具有一些有益作用。