The effects of candesartan on atherosclerosis in hyperlipidemic male rabbit induced by atherogenic diet

الملخص EN

Atherosclerosis is a disease of large and medium-sized muscular arteries and is characterized by endothelial dysfunction, vascular inflammation, and the build up of lipids, cholesterol, calcium, and cellular debris within the intima of the vessel wall.

This buildup results in plaque formation, vascular remodeling, acute and chronic luminal obstruction, abnormalities of blood flow, and diminished oxygen supply to target organ.

Candesartan exert a potent anti inflammatory activity.

Objectives : The objective of present study was to assess the effect of candesartan on atherosclerosis via interfering with inflammatory and oxidative pathways.

Method : 24 local domestic rabbits were assigned to 3 groups : Group I (n = 8), control ; Group II (n = 8), Rabbit fed 1 % cholesterol-diet (induced untreated group) ; Group III (n = 8), 1 % cholesterol-diet + candesartan (0.5 mg / kg / daily orally).

Blood samples were collected at (0 time), after 6 and after 12 weeks on experimental diets for measurement of serum triglycerides (TG), total cholesterol (TC), HDL-C and serum high sensitive C-Reactive Protein (hsCRP), serum IL-6 and serum TNF-a.

At the end of 12 weeks the aorta was removed for histopathology and histomorphometry to assess the atherosclerotic change according to American Heart Association classification of atherosclerosis phases and for aortic intema-media thickness also for aortic malondialdehyde (MDA) and reduced glutathione (GSH).

Results : Compared with the control, levels of TC, TG, LDL-C, VLDL-C, atherogenic index, hsCRP ,IL-6 ,TNF-a and aortic MDA were increased and aortic GSH and serum HDL-C were decreased in the animals with a high-fat diet (P < 0.01).

Histologically all induced-untreated rabbit showed significant atherosclerosis lesions (P < 0.05).

Candesartan treated groups showed significant effects on lipid parameters in comparing with induced untreated group (P < 0.05).

Candesartan counteract the change in hsCRP, IL-6, TNF-a and MDA in compare with induced untreated group (P < 0.01).

Candesartan prevent decrease tissue GSH level (P < 0.01) Morphologic analysis revealed that candesartan markedly reduced (P < 0.05) the severity of atherosclerotic lesion in the aorta compared with rabbits on a high-fat diet alone and decreases aortic intima-media thickness in histomorphometric measurements.

Conclusion : The results of the present study reveal that Candesartan prevented atherosclerosis in hypercholesterolemic rabbit via inhibition of inflammatory and oxidative pathways and reduced level of lipid parameters and decreased aortic intimamedia thickness.