THE COMPARATIVE EFFECT

Hypertension and diabetes mellitus frequently coexist, significantly increasing cardiovascular disease risk due to dyslipidemia, oxidative stress, and endothelial dysfunction. This study investigates the impact of co-administering losartan/metformin (L/M) and losartan/glibenclamide (L/D) on plasma and cardiac lipid profiles in L-NAME/streptozotocin (STZ)-induced hypertensive/diabetic male Wistar rats, with a focus on total cholesterol, triglycerides, HDL-cholesterol, and LDL-cholesterol. Fifty-two male Wistar rats (50–80 g) were housed under standard laboratory conditions and acclimatized for two weeks. Hypertension was induced by administering L-NAME (40 mg/kg) in drinking water for four weeks, while diabetes was induced via a single intraperitoneal injection of STZ (50 mg/kg). Successful induction was confirmed by systolic blood pressure measurement (tail-cuff method) and fasting blood glucose levels >200 mg/dL. The rats were divided into six groups (n=6 per group): control, untreated, diabetic treated with L/M, and diabetic treated with L/D. Drug administration was conducted orally for 28 days. At the end of the treatment period, rats were sacrificed via cervical dislocation. Blood samples were collected via cardiac puncture into EDTA-coated tubes, centrifuged at 3,000 rpm for 10 minutes, and plasma was stored at −20°C for lipid profile analysis. Cardiac tissues were excised, homogenized in phosphate-buffered saline (PBS), and centrifuged to obtain supernatants for further analysis. Plasma and cardiac total cholesterol levels did not significantly differ between groups (p > 0.05). The hypertensive/diabetic group exhibited reduced HDL-cholesterol (85.0 ± 19.2 mg/dL) compared to the normotensive/non-diabetic control (110.8 ± 2.1 mg/dL). Treatment with L/D showed the highest HDL levels (2.87 ± 2.71 mg/dL), suggesting a possible beneficial effect of glibenclamide on HDL metabolism. Triglyceride levels varied significantly (p < 0.05), with hypertensive/diabetic rats showing elevated plasma (160.0 ± 27.2 mg/dL) and cardiac (27.92 ± 12.55 mg/dL) triglycerides compared to controls. L/M treatment reduced plasma triglycerides to 145.2 ± 17.7 mg/dL, while L/D increased them to 180.3 ± 51.0 mg/dL, suggesting metformin’s superior role in mitigating hypertriglyceridemia. Plasma LDL-cholesterol levels remained unchanged across all groups (p > 0.05), indicating limited effects of these drug regimens on LDL metabolism. This study highlights the differential impact of losartan/metformin and losartan/glibenclamide co-administration on lipid metabolism in hypertensive/diabetic rats. These findings contribute to optimizing therapeutic strategies for managing dyslipidemia in comorbid hypertension and diabetes