الفهرس 
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Abstract
Visceral obesity is a risk factor for cardiovascular disease and it is becoming a dramatic issue for national health systems. Overweight and obesity are highly associated with multiple comorbidities, elevated blood pressure values, dyslipidaemia and reduced insulin sensitivity. Activation of the renin-angiotensin system (RAS) in adipose tissue may represent an important link between obesity and hypertension.
Angiotensin-converting enzyme 2 (ACE2)/Ang II/Ang 1–7 and apelin/APJ are two important peptide systems with diverse and fundamental cardiovascular protective effects that may prevent or reverse a variety of vascular and cardiac disorders.ACE2 is a mono carboxy peptidase which effectively plays a key role as the central negative regulator of the renin-angiotensin system (RAS). ACE2 is of particular interest because it is an essential component of RAS which is possibly implicated in metabolizing angiotensin (Ang) II into Ang 1–7
Angiotensin II has been shown to play a role in adipocyte growth and differentiation. Angiotensin II (Ang II), the physiologically-active product of the renin-angiotensin system (RAS), has been found to be an adipokine secreted by adipocytes. Ang II is known to exert its effects mainly via angiotensin II receptor type 1 (AT1R).Apelin, another adipokine has been found able to restore glucose tolerance in obese and insulin-resistant mice. Because they are both involved in metabolic disorders, there may be an interaction between the two adipokines.
Apelin has been identified as the endogenous ligand of the G protein–coupled receptor APJ. Apelin and APJ mediate a wide range of physiologic actions, including angiogenesis, heart contractility and blood pressure regulation and other effects. Apelin and APJ are expressed on the newly developing blood vessels during angiogenesis. Apelin elicits endothelium-dependent, nitric oxide-mediated vasorelaxation and reduces arterial blood pressure.
Blockage of the RAS with either angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker results in a substantial increase in apelin levels and lowering blood pressure.
Aim of the work
1- To investigate the role renin-angiotensin system(RAS) in obesity associated hypertension.
2- To determine the role of apelin in obesity& hypertension.
3- To assess the role of NO as a possible mechanism of action for both Apelin and Ang 1-7.
4- To clarify the possible interactions between (RAS) system and apelin/APJ system.
Materials& methods
Sixty three rats were used in this study divided into 3main groups, group I given standard rat chow, group II given high fat sucrose diet(HF-HS) for 4 weeks, group III given high fat sucrose diet for 10 weeks. Each group was further divided into 3subgroups (n=7), non- treated groups not given any drugs (group1,4,7), ACEI groups given captopril 40 mg/kg orally daily (group2,5,8), L-NAME groups given L-NAME (20mg/kg) I.V daily(group3,6,9).
At the end of experiment:
BMI was calculated and systolic blood pressure was measured.
Blood samples were collected for measurement of blood glucose & TG.
Rats were scarified by decapitation for collection of visceral adipose tissue (epididymal fat) for gene expression of AT1R, ANG1-7/Mas R, apelin/APJ R and VEGF.
Results:
Results of this study demonstrated activation of the adipose (RAS) and Apelin/APJ system in rats with diet-induced obesity and hypertension, consistent with a strong link between visceral obesity and hypertension.
Obesity due to HF-HS diet was associated with hyperglycemia, hypertriglecridemia and hypertension. This was associated with marked upregulation in AT1R,apelin R & VEGF expression and downregulation of Ang 1-7 R in adipose tissue. The previous effects significantly increased with prolonged HF-HS ingestion for 10 weeks.
Captopril caused significant decrease in BMI, blood pressure, blood glucose and serum triglycerides associated with upregulation of Ang1–7& apelin/APJ in adipose tissue. L-NAME given to obese rats aggravated hypertension.
Conclusion:
from our results we can conclude that, Obesity induced hypertension (after 10 weeks of HF-HS) was associated with increased AT1 &apelin receptor expression and decreased Ang 1-7 receptor expression which provides evidence that apelin (vasodilator adipokine) could not antagonize hypertensive effect of AngII/AT1R. This may be explained by apelin resistance or high expression of Ang II.
However, after 4 weeks of HF-HS, hypertension did not develop which may be partly explained by apelin antagonistic effect of Ang II (apelin can overcome and counteract harmful effect ofAng II) but this effect failed with chronic obesity.
from our results we can also conclude that obesity due to HF-HS diet was associated with increased VEGF i.e. obesity is vascular dependent and that apelin increase adipose tissue growth through increasing vascularity.
The current results also confirmed that, blockers of the RAS are high-efficacy drugs in the treatment of obesity-induced hypertension as they provide benefits against several aspects of the metabolic syndrome. Captopril (ACEI) prevented the development of obesity induced hypertension as it caused significant decrease in blood pressure& serum triglycerides through increased Ang 1-7/Mas R and Apelin/APJ receptor expression.
L-NAME even in small dose, aggravated obesity induced hypertension, through antagonizing apelin and Ang 1-7 vasodilator action& increasing AT1 expression.