Efectos de irbesartán y losartán en conejos hipercolesterolémicos

Abstract

Introduction and objectives This study was performed to examine the long-term effects of irbesartan and losartan, two angiotensin (AT1) receptor antagonists, on lipoproteins and vascular responsiveness in vessels isolated from hypercholesterolemic rabbits. Material and methods Four groups of rabbits (n = 40) were used: group 0 (control group; n = 10); group 1 (hypercholesterolemic group, 0.5% [wt/wt] cholesterol-enriched diet; n = 10); group 2 (hypercholesterolemic + irbesartan 10 mg/kg/day; n = 10), and Group 3 (hypercholesterolemic + losartan 10 mg/kg/day; n = 10). The animals were maintained for 18 weeks. Results After 18 weeks of treatment levels of total cholesterol (TC) and low density lipoproteins (LDL) in irbesartan and losartan treated groups were significantly lower than those of Group 1 (α = 0.05; p < 0.05 and p < 0.01, respectively). Furthermore, levels of high density lipoproteins (HDL) were higher in the treated groups than in the hypercholesterolemic (α = 0.05; p < 0.05 and p < 0.01, respectively) when we consider the same level of total cholesterol in the hypercholesterolemic and the treated groups. Despite the effect of the drugs on the above mentioned parameters, treatment with irbesartan or losartan did not improve endotheliumdependent and independent relaxation in aortic and mesenteric rings. Treatment with irbesartan and losartan decreased NA-induced contraction in aortic rings with respect to the hypercholesterolemic group (α = 0.05; p < 0.05). In addition, irbesartan treatment improved the increase in serotonin-induced contraction in proximal coronary arteries with respect to the hypercholesterolemic group (α = 0.05; p < 0.001). Conclusions These results indicate that irbesartan and losartan restore NA-induced contraction in hypercholesterolemic rabbit-isolated arteries and improve lipoprotein profile in cholesterol-fed rabbits.