Antihypertensive and antihyperglycemic effects of combinations of losartan with metformin and/or glibenclamide in desoxycorticosterone acetate and streptozotocin-induced hypertensive diabetic rats.

Abstract

Background: Hypertension is a medical condition that often comorbidly exist in patients with type II diabetes. Therefore, it is very important to manage both conditions simultaneously to mitigate the complications and mortality connected with this comorbidity. Hence, this study investigated the antihypertensive and antihyperglycemic effects of combinations of losartan (LOS) with metformin (MET) and/or glibenclamide (GLB) in hypertensive diabetic rats. Hypertensive diabetic state was induced with desoxycorticosterone acetate (DOCA) and streptozotocin (STZ) in adult Wistar rats. The rats were divided into 5 groups (n = 5): control group (group 1), hypertensive diabetic (HD) control (group 2), treatment groups receiving LOS + MET (group 3), LOS + GLB (group 4), and LOS + MET + GLB (group 5). Group 1 comprised healthy rats while groups 2-5 were HD rats. The rats were treated orally once daily for 8 weeks. Fasted blood glucose (FBS) level, haemodynamic parameters, and some biochemical indices were thereafter assessed.

Results: FBS level and blood pressure measurements were significantly (P < 0.05) increased following induction by DOCA/STZ. The drug treatment combinations, particularly combination of LOS + MET + GLB, significantly (P < 0.05) reduced the induced hyperglycemia and remarkably decreased systolic blood pressure and heart rate. There was significant (P < 0.05) reduction in raised lactate dehydrogenase and creatinine kinase levels by all drug treatment combinations except LOS + GLB.

Conclusions: Our findings suggest that LOS combinations with MET and/or GLB exhibited significant antidiabetic and antihypertensive effects against DOCA/STZ-induced hypertensive diabetic state in rats.