Murali B, Umrani Dhananjay N, Goyal Ramesh K
Department of Pharmacology, L.M. College of Pharmacy, Ahmedabad, India.
Mol Cell Biochem. 2003 Jul;249(1-2):85-90.
The present investigation was undertaken to study the effect of chronic treatment with angiotensin (AT1) receptor antagonist losartan (2 mg/kg, p.o., 6 weeks) on streptozotocin (STZ) induced (45 mg/kg, i.v., single dose) renal dysfunctions in diabetic rats. Injection of streptozotocin produced not only the cardinal symptoms of diabetes mellitus like loss of body weight, hyperglycemia, and hypoinsulinemia but also the renal dysfunctions. Losartan treatment significantly prevented all these changes except STZ-induced hypoinsulinemia. There was a significant elevation of blood pressure in diabetic rats and treatment with losartan significantly brought it back to normal. Renal dysfunction in diabetic rats was characterized by a significant decrease in creatinine clearance, elevated levels of electrolytes and renal hypertrophy. Treatment with losartan prevented these changes. A good correlation was found between biochemical parameters and histopathological abnormalities. Our data suggests that, losartan may be considered as the drug of choice when there is a co-existence of diabetes mellitus and hypertension with compromised kidney function.
本研究旨在探讨血管紧张素(AT1)受体拮抗剂氯沙坦(2毫克/千克,口服,6周)长期治疗对链脲佐菌素(STZ)诱导(45毫克/千克,静脉注射,单次剂量)糖尿病大鼠肾功能障碍的影响。注射链脲佐菌素不仅产生了糖尿病的主要症状,如体重减轻、高血糖和低胰岛素血症,还导致了肾功能障碍。氯沙坦治疗显著预防了所有这些变化,但STZ诱导的低胰岛素血症除外。糖尿病大鼠血压显著升高,氯沙坦治疗显著使其恢复正常。糖尿病大鼠的肾功能障碍表现为肌酐清除率显著降低、电解质水平升高和肾肥大。氯沙坦治疗预防了这些变化。生化参数与组织病理学异常之间存在良好的相关性。我们的数据表明,当糖尿病和高血压并存且肾功能受损时,氯沙坦可被视为首选药物。