Comparative study of cardiovascular effects of losartan and captopril in rabbits

ABSTRACT

Drugs that interfere with renin - angiotensin system [RAS] play a prominent role in treatment of cardiovascular diseases. These drugs include two groups, angiotensin converting enzyme inhibitors e.g. captopril and angiotensin II receptor blockers e.g. losartan. This work was performed to investigate the effects of chronic administration [60 days] of each of losartan and captopril on the progression of atherosclerosis, serum lipids, glutathione peroxidase activity and on arterial blood pressure in rabbits fed with 1% cholesterol enriched diet. Specimens from different levels of aorta, heart, liver and kidneys of each rabbit were formalin-fixed, paraffin-embedded and stained with haematoxylin and eosin and Verhoff's stains. The serum lipids were estimated by enzymatic colorimetric tests. The glutathione peroxidase activity in the aortic tissues was determined by a modified spectrophotometric method. Our results showed that administration of each of losartan and captopril had the ability to attenuate the progression of atherosclerosis in hypercholesterolemic rabbits. The antiatherogenic effect of losartan was more pronounced than that of captopril. Both drugs also prevented the effect of hypercholesterolemia on the heart and liver compared to the non-medicated hypercholesterolemia rabbits. On the other hand, cholesterol-fed rabbits treated with each of losartan and captopril demonstrated significant decrease in total cholesterol, triglycerides and low density lipoprotein with an insignificant increase in high density lipoprotein compared to untreated hypercholesterolemia rabbits. However, the intensity of changes produced by losartan was of greater extent than that produced by captopril. This study revealed an increase in the glutathione peroxidase activity in aortic tissues of groups of atherosclerotic animals treated with either losartan or captopril in comparison with the non-mediated atherosclerotic rabbits. Moreover, a lowering in the blood pressure was recorded in cholesterol-fed rabbits treated with either losartan or captopril. In conclusion, these results are encouraging and the beneficial antiatherosclerotic effects of both drugs are presumably attributed to then ability to interrupt influences on the RAS. In addition, their contributory role of the possible antioxidant properties of these drugs must not be ruled out. Besides, the documented ability of these drugs to accumulate kinins and nitric oxide as well as prevention of the vascular endothelial dysfunction can not be neglected