White adipose tissue (WAT) is now recognized as the largest endocrine organ of the body. WAT secretes a number of bioactive peptides and proteins, collectively termed “adipokines”. Adipokines have different biological effects, including blood pressure control. Dysregulated production and release of specific adipokines, namely renin angiotensin system (RAS) peptides &apelin, from WAT in the setting of obesity may contribute to hypertension. Based on previous concepts, the present study aimed to clarify role of RAS and Apelin/APJ system in obesity-induced hypertension through modulation of Angiotensin type 1 receptor (AT1R), Angiotensin 1-7/Mas receptor and Apelin/ APJ receptor expression and to elucidate the possible interaction between the two systems. 48rats were used in this study divided into 6 groups, group 1(control group) given standard rat chow, group 2(control + captopril group):given standard rat chow + captopril 40mg/kg, group 3(Control + L-NAME group): given standard rat chow + L-NAME 20mg/kg, group 4(control hypertensive group):fed high fat high sucrose diet (HF-HS) for 10 weeks, Group 5: (hypertensive + captopril group): Fed HF-HS diet & received captopril (40mg/kg) for 10weeks, Group 6: (hypertensive + LNAME group): Fed HF-HS diet & received L-NAME (20mg/kg) for 10 weeks. At the end of experiment, body weight, fat weight and systolic blood pressure were measured. Visceral adipose tissue (epididymal fat) was collected for gene expression of AT1R, Ang1-7 R and apelin/APJ. Results of this study demonstrated activation of the adipose (RAS) and Apelin/APJ system in rats with diet-induced hypertension, consistent with a strong link between visceral obesity and hypertension. Obesity induced hypertension was associated with marked upregulation in AT1R, apelin /APJ R expression and down regulation of Ang-(1-7)/Mas R in adipose tissue. Captopril treatment showed significant decrease in body weight, fat weight and systolic blood pressure associated with significant increase in adipose tissue gene expression of Apelin/APJ receptor and Ang 1-7/Mas receptor. Whereas L-NAME significantly increased blood pressure and decreased body weight, fat weight with significant increased AT1R expression. Obesity induced hypertension was associated with increased AT1R & apelin receptor expression and decreased Ang-(1-7) R expression which provides evidence that apelin/APJ upregulation by HFHS diet could not antagonize hypertensive effect of AngII/AT1R. This may be explained by apelin resistance or high expression of Ang II. ACE inhibition decreased blood pressure significantly in obese hypertensive rats through increased Ang-(1-7) R & apelin/APJ receptor expression. L-NAME raised blood pressure significantly in obese rats through increased AT1R expression and possible inhibition of nitric oxide (NO)- mediated vasodilator action of Ang-(1-7) &apelin. These results suggest an interaction between Apelin and RAS peptides to regulate ABP in obese subjects.
