الفهرس | Only 14 pages are availabe for public view |
Abstract Hypertension and DM are considered to be important risk factors for cardiovascular morbidity and mortality. Efficient antihypertensive therapy in diabetic patients should not only reduce the increased BP but also reduce the diabetes-induced cardiovascular changes, such as macrovascular and microvascular complications together with satisfactory control of hyperglycemia. The present study aimed to investigate the possible beneficial effect(s) of combination of aliskiren with either perindopril or losartan on pharmacological and biochemical parameters in hypertensive diabetic albino rats, together with histopathological changes in heart and kidney of these rats. The target of these combinations was to provide an attempt to perform a complete block of reninangiotensin- aldosterone pathway that would provide a possible reduction in either or both cardiac and renal complications in them. The present work showed that chronic treatment of hypertensive diabetic rats with aliskiren alone or in combination with either perindopril or losartan produced significant increase in LVEDP and LV dP/dtmax and significant decrease in invasive mean ABP but without significant difference between the treated groups. Thus, no further benefit was noticed in the combination therapy especially in additional lowering of the elevated BP. Regarding the effect on ECG, results were conflicting in DOCA-STZ untreated group and all treated groups due to hyperkalemia. Also, the present work showed that chronic treatment with aliskiren alone or in combination with either perindopril or losartan produced non significant difference in blood glucose level in these rats. Thus the combination therapy did not add any additional benefit in modulating the high blood glucose. The combination therapy also showed higher serum potassium and creatinine levels than aliskiren monotherapy but there was non significant difference in TBARS level in heart and kidney homogenates in the hypertensive diabetic albino rats. As regard the histopathological changes in the heart of these hypertensive diabetic rats, chronic treatment with aliskiren alone or in combination with losartan showed more packed cardiac muscle fibers with some increase in cellularity while aliskiren combination with perindopril showed showed separation of cardiac muscle fibers with congested capillaries and increase in inflammatory cells and fibrous tissue between them. As regard the histopathological changes in the kidney of these rats, chronic treatment with aliskiren alone or in combination with losartan showed congestion of peritubular capillaries and reduction of interstitial fibrosis while aliskiren combination with perindopril showed disruption in the kidney structure and increase in interstitial fibrosis. Conclusion It is concluded from the previous findings that although the idea of adding aliskiren to ACEI or ARB theoretically achieve tighter RAAS inhibition, this combination therapy in hypertensive diabetic rat model did not add any significant additional benefit regarding improvement of either or both selected cardiac and renal functions. Furthermore; combination therapy failed to achieve normalization of mean BP compared to aliskiren monotherapy, probably due to deterioration of renal functions. |