Comparative Evaluation of Carvedilol, Metoprolol and Atenolol on Cardiovascular Complications Associated with Experimental Type 2 Diabetes

Abstract

Objective- Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with type 2 diabetes. β- receptor blockers provide cardiovascular protection in diabetic patients. We have studied the effect of 8 weeks treatment with carvedilol, metoprolol and atenolol on cardiovascular complications associated with streptozotocin (STZ) induced diabetes in neonatal rats. Materials and methods- Wistar rats of 5 day age were made diabetic with STZ (80 mg kg-1, ip). Various biochemical, cardiac parameters and hemodynamic parameters were measured at the end of 8 weeks of treatment with carvedilol (1mg/kg/day, p.o.), metoprolol (10mg/kg/day, p.o) and atenolol (10mg/kg/day, p.o) like general parameters (body weight, food intake and water intake), glucose and insulin levels, cholesterol, triglyceride, very low density lipoproteins, atherogenic index and high density lipids, creatinine kinase and lactate dehydrogenase enzyme and C-reactive protein (CRP) levels, heart rate, blood pressure, rate of pressure development and decay, cardiac hypertrophy and antioxidant levels. Results- STZ produced hyperglycemia, hyperinsulinemia, hyperlipidemia, increased blood presser, increased creatinine kinase and lactate dehydrogenase enzymes and C-Reactive protein (CRP) levels, reduction in heart rate, blood presser, cardiac hypertrophy. Chronic treatment with carvedilol and metoprolol significantly (P<0.05) prevented STZ induced hypertension, hyperglycemia and hyperinsulinemia. Atenolol did not produce reduction in hyperglycemia and hyperinsulinemia. Carvedilol and metoprolol significantly (P<0.05) reduced the elevated cholesterol, very low density lipoprotein (VLDL), atherogenic index and triglyceride levels in diabetic rats and increased the lower high density lipoprotein (HDL)-cholesterol levels while atenolol showed no significant effect on lipid profile. Further, all drugs produced a significant (P<0.05) reduction in the elevated levels of CRP and other cardiac enzyme markers like Lactate de-hydrogenase and creatinine kinase of diabetic rats. STZ-induced bradycardia was also prevented by carvedilol and metoprolol treatment and atenolol showed no significant (P<0.05) effect on heart rate. All three drugs produced beneficial effect by preventing cardiac hypertrophy as evident from cardiac hypertrophy index and left ventricular hypertrophy.Carvedilol prevent STZ induced oxidative stress but metoprolol and atenolol showed no significant (P<0.05) effect on antioxidant levels. Conclusion- Our data suggests that carvedilol and metoprolol have beneficial effect in cardiovascular complications associated with streptozotocin (STZ) induced diabetes in neonatal rats as depicted by prevention of hyperglycemia, hyperinsulinaemia, hyperlipidemia, hypertension, bradycardia, cardiac and left ventricular hypertrophy and reduction in cardiac biomarker levels. Further, carvedilol appears to be more beneficial than metoprolol since it also prevents oxidative stress. However, atenolol shows no beneficial effect on diabetes induced cardiovascular complications.