الفهرس 
Introduction and Aim of the WorkOnly 14 pages are availabe for public view
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Abstract
Hypertension, with a prevalence of up to 30% throughout the world, is increasing in incidence in more affluent and aging populations. Because it is totally asymptomatic, it has been named the ”silent killer,” as it is the major contributor-or risk factor-to cardiovascular morbidity and mortality.
In response to elevated pressure, the ventricular hypertrophy compensates for the increased wall stress. However, the ventricular hypertrophy involves numerous structural adaptations that may lead to ventricular dysfunction and, eventually, heart failure. Particular emphasis is placed on molecular mechanisms that govern the development of hypertrophy and that may lead to maladaptive structural changes resulting in adverse cardiac events.
The present study aimed mainly to:
1- Shed light on the characteristic features of cardiac remodeling resulted from chronic hypertension. Particularly left ventricular hypertrophy (LVH) and to address the molecular mechanisms underlying them.
2- Evaluate the protective effect of Val and Ali either as monotherapy or in combination form in modulating cardiac complications in hypertensive rats and comparing between combined and individual therapy
3- Investigate the possible correlations between the studied biochemical parameters.
4- Elucidate the histopathological and immunohistochemical changes in cardiac tissue following supplementation of Val and Ali individually or in a combined form.
Selected parameters to fulfill such requirements:
Hemodynamic parameters: Mean arterial blood pressure (MAP) and heart weight/body weight (Hwt/Bwt) ratio.
Biochemical parameters:
1- In serum: Total cholesterol (TC), high denisty lipoprotein cholesterol (HDL-c), low denisty lipoprotein cholesterol (LDL-c) and triacyl glycerol (TAG).
2- In cardiac Tissue: Superoxide dismutase (SOD), glutathione peroxidase (GPx), angiotensin converting enzyme (ACE), atrial natriuretic peptide (ANP), α- myosin heavy chain (α-MHC), β- myosin heavy chain (β-MHC) and regulator of calcineurin-1 (RCAN-1) gene expressions.
Immunohistochemical study: Immunohistochemical detection of inducible nitric oxide synthase (iNOS) and nuclear factor Kappa-B (NF-κB).
Histopathological study:
Representative samples of rat ventricular tissues were processed for histological examination under the light microscope, to configurate tissue changes and explore their possible correlations with the selected biochemical parameters.
Experimental design:
Induction of hypertension:
One week after acclimization, one hundred and twenty rats were anaesthetized using intra-peritoneal injection of sodium pentobarbital (80mg/kg). In rapid succession, each rat was fixed in the lateral position on the operating table and the abdominal skin was shaved and sterilized with 70% ethyl alcohol, then, the abdominal wall was opened by an incision along the mid line and the left kidney was exposed. A short segment of the left renal artery was isolated by blunt dissection and a standard silver clip (120mm gap) was placed around the renal artery. The kidney was returned to the retroperitoneal cavity, muscle and skin layers of the abdominal wall were sutured.
Rats were allowed to recover from surgery in a warmed cage for 1:2 hours. Prophylactic antibiotic pencillin G- sodium was given by intramuscular injection. Five days later arterial blood pressure was measured. Rats achieved B.P more than 90 mmHg were selected for this study as hypertensive animals.
The current study was carried on two main groups.Normal rats (NC):
They were supplied with chew diet (n=30).Hypertensive rats:
They were subdivided into 4 subgroups:Hypertensive control subgroup (HC):
Received water daily for 4 weeks and utilized as hypertensive control, (n=30).Valsartan treated subgroup (Val):
Hypertensive rats treated with Val (8mg/kg/day) for four weeks, (n=30).Aliskiren treated subgroup (Ali):
Hypertensive rats treated with Ali (25mg/kg/day) for four weeks, (n=30).