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Abstract This work aimed to study the effect of atorvastatin (HMGCoA reductase inhibitor), losartan (angiotensin II antagonist) and ramipril(angiotensin converting enzyme inhibitor) on total cholesterol,triglyceride, LDL, HDL, blood glucose, MDA, NT, AGEPs, renal haemodynamics, arterial blood pressure and aortic contractile response in hypercholesterolemic hyperglycemic rats . Fifty male albino rats of local strain weighing (130-180 gm) were used in this study. These animals were subdivided into two main groups : Group 1, which consisted of 10 rats and served as normal control group, group2 which consists of 40 rats (hypercholesterolemic hyperglycemic group) and further subdivided into four equal subgroups: Subgroup 2a , which received normal saline only, subgroup 2b which treated with atorvostatin 2.5 mg/kg/day for one month by intragastric tube , subgroup 2c which treated with losartan (3mg/kg/day) for one month by intragastric tube and subgroup 2d which treated with ramipril ( 0.3 mg/kg/day ) for one month by intragastric tube . Hypercholesterolemia was induced in albino rats by taking 2% cholesterolemic enriched diet for 2 months and hyperglycemia was induced by an intraperitoneal injection of a single dose of STZ (40mg/Kg) after an 18 hours fasting. The serum lipids, blood glucose,MDA, NT and AGEPs was laboratory estimated, the systolic and mean blood pressure was monitored with rat-tail plethysmography and pneumatic pulse transducer. The renal blood flow velocity and the renal vascular resistance were measured by pulsed blood flowmeter(Doppler). The rat aortic strip preparations were used to estimate changes of vascular reactivity to NE . It was found that atorvastatin produced significant reduction in total cholesterol, LDL, triglyceride, blood glucose, MDA, NT, AGEPs but significantly increase in HDL serum level compared with hypercholesterolemic hyperglycemic rats. Also, it produced significant reduction in both systolic and mean arterial blood pressure. Moreover, it produced significant reduction in PI, RP, HR and significant increase in renal blood flow compared with hypercholesterolemic hyperglycemic rats. Regarding the isolated rat aorta, it also produced significant reduction in response to MEC, EC50 and MR of NE compared with hypercholesterolemic hyperglycemic rats. As regard losartan , it was founded that it produced significant reduction in total cholesterol, LDL, triglyceride, blood glucose, MDA,NT, AGEPs but significantly increase in HDL serum level compared with hypercholesterolemic hyperglycemic rats. Also, it produced significant reduction in both systolic and mean arterial blood pressure. Moreover, it produced significant reduction in PI, RP, HR and significant increase in renal blood flow compared with hypercholesterolemic hyperglycemic rats. Regarding the isolated rat aorta, it also produced significant reduction in response to MEC, EC50 and MR of NE compared with hypercholesterolemic hyperglycemic rats. Ramipril produced significant reduction in total cholesterol, LDL,triglyceride, blood glucose, MDA, NT, AGEPs but significantly increase in HDL serum level compared with hypercholesterolemic hyperglycemic rats. |