Department of Pharmacology, L. M. College of Pharmacy, Ahmedabad, Gujarat, India.
J Cardiovasc Pharmacol. 2009 Dec;54(6):502-9. doi: 10.1097/FJC.0b013e3181be75cc.
We have studied the effect of 8-week treatment with spironolactone (20 mg*kg(-1)*day(-1)) on cardiovascular complications associated with streptozotocin (STZ)-diabetic rats. Wistar rats were made diabetic with STZ (45 mg/kg, intravenously). Various biochemical and cardiac parameters were measured at the end of 8 weeks. STZ produced hyperglycemia; hypoinsulinemia; hyperlipidemia; increased blood pressure; increased creatinine, cardiac enzyme, and C-reactive protein levels; reduction in heart rate; and cardiac hypertrophy. Chronic treatment with spironolactone significantly prevented STZ-induced bradycardia, hypertension, and elevated fasting glucose level with simultaneous increase in serum insulin levels. It significantly reduced the elevated cholesterol, very-low-density lipoprotein, and triglyceride levels and increased the lower high-density lipoprotein-cholesterol levels in diabetic rats. Furthermore, spironolactone also produced a significant reduction in the elevated creatinine levels, C-reactive protein, and levels of lactate dehydrogenase and creatinine kinase. It also produced beneficial effect in diabetic rats by preventing cardiac hypertrophy as evident from decrease in left ventricular collagen levels, cardiac hypertrophy index, and left ventricular hypertrophy index. Our data suggest that spironolactone prevents not only the STZ-induced metabolic abnormalities but also cardiovascular complications.
我们研究了螺内酯(20mg*kg(-1)*day(-1))治疗 8 周对链脲佐菌素(STZ)-糖尿病大鼠相关心血管并发症的影响。Wistar 大鼠用 STZ(45mg/kg,静脉注射)制成糖尿病模型。8 周结束时测量各种生化和心脏参数。STZ 导致高血糖;胰岛素减少;高血脂;血压升高;肌酐、心脏酶和 C 反应蛋白水平升高;心率下降;心肌肥大。螺内酯的慢性治疗显著预防了 STZ 诱导的心动过缓、高血压和空腹血糖升高,同时增加了血清胰岛素水平。它显著降低了糖尿病大鼠升高的胆固醇、极低密度脂蛋白和甘油三酯水平,并增加了较低的高密度脂蛋白胆固醇水平。此外,螺内酯还显著降低了升高的肌酐水平、C 反应蛋白和乳酸脱氢酶和肌酸激酶水平。它还通过降低左心室胶原水平、心脏肥大指数和左心室肥大指数来预防糖尿病大鼠的心脏肥大,从而产生有益的效果。我们的数据表明,螺内酯不仅可以预防 STZ 引起的代谢异常,还可以预防心血管并发症。