Sevak A R, Goyal R K
Department of Pharmacology, L.M. College of Pharmacy, Navrangpura, Ahmedabad, India.
Pharmacol Res. 1996 Nov-Dec;34(5-6):201-9. doi: 10.1006/phrs.1996.0089.
The present study was undertaken to study the effects of chronic treatment with lisinopril on the cardiovascular complications in streptozotocin (STZ) diabetic and deoxycorticosteroneacetate (DOCA) hypertensive rats. Injection of STZ produced severe glycosuria (> 2%), hyperglycemia, hypoinsulnaemia, polydypsia, polyphagia and loss of body weight. It also produced hypothyroidism, hypercholesterolaemia, hypertriglyceridaemia, hypertension, bradycardia and decreased left ventricular developed pressure (LVDP). Elevation in serum creatinine level and increased activity of liver enzymes were also found in STZ treated animals. DOCA by itself did not produce any change in blood glucose but reduced serum insulin levels in non-diabetic animals. However, in the diabetic group, DOCA reduced blood sugar levels. Treatment of STZ-diabetic rats with DOCA did not aggravate cardiac depression or hyperglycaemia. Treatment of rats with lisinopril (1 mg kg-1, p.o. daily for six weeks), in diabetic and diabetic hypertensive animals prevented STZ induced loss of body weight and hypertension, bradycardia and hypothyroidism. It also prevented STZ induced hyperglycemia and hypoinsulinaemia in both diabetic and diabetic hypertensive animals. There was a reduction in cholesterol, triglyceride, and LDL levels; the ratio between total cholesterol to HDL and LDL to HDL and an improvement in LVDP at higher filling pressure in diabetic as well as diabetic hypertensive animals. Treatment with lisinopril also prevented hypertrophy and elevated levels of serum creatinine, SGOT and SGPT in diabetic animals. In conclusion, the present data suggests that STZ-DOCA model may not be considered as the ideal model for the study of cardiovascular complications of combined treatment hypertension and diabetes. However, the present investigation presents a number of beneficial effects of lisinopril treatment in diabetic with or without hypertensive rats and it may be considered as one of the drugs of choice in treatment of hypertension when it is associated with diabetes mellitus.
本研究旨在探讨赖诺普利长期治疗对链脲佐菌素(STZ)诱导的糖尿病大鼠和醋酸脱氧皮质酮(DOCA)诱导的高血压大鼠心血管并发症的影响。注射STZ可导致严重糖尿(>2%)、高血糖、低胰岛素血症、多饮、多食和体重减轻。还可引起甲状腺功能减退、高胆固醇血症、高甘油三酯血症、高血压、心动过缓和左心室舒张末压(LVDP)降低。STZ处理的动物血清肌酐水平升高,肝酶活性增加。DOCA本身对血糖无影响,但可降低非糖尿病动物的血清胰岛素水平。然而,在糖尿病组中,DOCA可降低血糖水平。用DOCA治疗STZ糖尿病大鼠不会加重心脏抑制或高血糖。用赖诺普利(1mg/kg,口服,每日一次,共六周)治疗糖尿病和糖尿病高血压大鼠,可预防STZ诱导的体重减轻、高血压、心动过缓和甲状腺功能减退。还可预防糖尿病和糖尿病高血压动物中STZ诱导的高血糖和低胰岛素血症。糖尿病和糖尿病高血压动物的胆固醇、甘油三酯和低密度脂蛋白水平降低;总胆固醇与高密度脂蛋白以及低密度脂蛋白与高密度脂蛋白的比值降低,且在较高充盈压下LVDP有所改善。赖诺普利治疗还可预防糖尿病动物的心肌肥厚以及血清肌酐、谷草转氨酶和谷丙转氨酶水平升高。总之,目前的数据表明,STZ-DOCA模型可能不是研究高血压合并糖尿病心血管并发症的理想模型。然而,本研究显示了赖诺普利治疗对糖尿病大鼠(无论有无高血压)的诸多有益作用,在高血压合并糖尿病时,赖诺普利可被视为治疗高血压的首选药物之一。