Effects of Inhibition of Angiotensin Converting Enzyme, Blocking Angiotensin Type 1 (AT1) Receptor, and Blocking Aldosterone Receptor on High Fat Fructose Diet Feeding Induced Changes in Lipid Profile, Blood Pressure
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- Category: Vol. 83, September 2015
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Effects of Inhibition of Angiotensin Converting Enzyme, Blocking Angiotensin Type 1 (AT1) Receptor, and Blocking Aldosterone Receptor on High Fat Fructose Diet Feeding Induced Changes in Lipid Profile, Blood Pressure, MOHAMED H.G.E. MOSTAFA, MOSHERA RATEB, MOHAMED E. SALEH and REHAM MOHAMED
Abstract
Objective: Increased consumption of fat and soft drinks rich in fructose is closely associated with a higher prevalence of metabolic syndrome. The major pathogensis of metabolic syndrome is the development of insulin resistance caused by accumulation of visceral fat which promotes the elevation of blood pressure, dyslipidemia and dysregulation of glucose metabolism. During the last decade, the existence of local Renin-Angiotensin System (RAAS) in adipose tissue and its functional importance has attracted greater attention. Hyper-activity of systemic and adipose tissue specific RAASs is associated with obesity, and the RAAS is implicated in the control of glucose homeostasis, providing a potential causal link among obesity, diabetes, and hypertension. The aim of this work was to investigate the effects of inhibition of angiotensin converting enzyme, blocking angiotensin II type 1 receptor, and blocking aldosterone receptor on High Fat Fructose Diet (HFFD) feeding induced-changes in lipid profile, blood pressure in male albino rats.
Material and Methods: 50 male albino rats with body weight 100-115gm were randomly divided into 5 groups. Each group contained 10 rats and with equal average body weights: Group I (control group) in which rats were fed standard rat chow for the entire study duration, Group II (HFFD) in which rats were fed HFFD for the entire study duration, Group III (HFFD+ ACE inhibitor) in which rats were fed HFFD and treated orally with angiotensin converting enzyme inhibitor, captopril, at a dose of 40mg/kg/day, for the entire study duration, Group III (HFFD+ AT1 blocker) in which rats were fed HFFD and treated orally with Angiotensin II Type 1 (AT 1) receptor blocker. Losartan, at a dose of 1 0mg/ kg/day for the entire study duration, Group V (HFFD+ Aldos-terone receptor blocker) in which rats were fed HFFD and treated orally with Aldosterone receptor blocker, aldactone, at a dose of 16mg/kg/day for the entire study duration. At the end of study period (10 weeks), rats were weighted then sacrificed. Serum was prepared for fasting triglycerides, cholesterol, HDL-cholesterol, Free fatty acids and blood pressure.
Results: This study showed that the rats fed HFFD (group II) for 10 weeks showed typical dyslipidemia (high serum triglycerides, total cholesterol, free fatty acids with significant decrease in HDL-cholesterol, moreover, blood pressure sig-nificantly increased compared to Group I. Results of the present work showed that inhibition of RAAS (by ACE inhibitor Captopril (group III), AT 1R blocker Losartan (Group IV), or mineralocorticoid receptor blocker Spironolactone (Group V) in rats fed HFFD can attenuate HFFD-induced changes as evident by significant decreases in mean values of fasting serum triglycerides, cholesterol, free fatty acids, with significant increase in HDL-cholesterol, Moreover, mean value of systolic blood pressure significantly decreased com-pared to group II. The ability of interference with RAAS to modify HFFD-induced changes is partial as evident by signif-icant increases in fasting serum triglycerides, cholesterol and free fatty acids, with significant decrease in HDL-cholesterol compared to control group. Moreover, mean value of systolic blood pressure significantly increased compared to Group I.
Conclusion: High fat fructose diet participates in the development of hyperlipidemia, and hypertension. Interference with RAAS system by inhibiting angiotensin converting enzyme, blocking angiotensin II type 1 receptor, or blocking aldosterone receptor can partially improve HFFD induced changes. In conclusion, the established role of both circulating and local RAAS on the pathogenesis of hyperlipidemia and hypertension, there is considerable interest on the effect of RAAS inhibitors since they are widely used, reasonably inexpensive, and with excellent safety profile. Despite the encouraging evidence from animal studies, data from human studies are limited and contradictory and most data are from retrospective studies. Accordingly, more studies are needed to directly assess the effectiveness of ACE inhibitor, ARBs, and mineralocorticoid blockers in obese subjects.