الفهرس 
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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.