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doi: 10.1016/S0214-9168(02)78868-2
Efectos de irbesartán y losartán en conejos hipercolesterolémicos
Effects of irbesartan and losartan in cholesterol-fed rabbits
E. Padilla, , M. Sanz, P. Ganado, T. Tejerina
Departamento de Farmacología. Facultad de Medicina. Universidad Complutense. Madrid
Resumen
Introducción y objetivos

Este estudio se realizó para examinar los efectos a largo plazo de irbesartán y losartán, dos antagonistas del receptor AT1 de la angiotensina, sobre el perfil lipídico y la reactividad vascular en vasos aislados de conejos hipercolesterolémicos

Material y métodos

Se usaron cuatro grupos de conejos (n = 40): grupo 0 (grupo control; n = 10); grupo 1 (grupo hipercolesterolémico, alimentado con una dieta enriquecida en colesterol al 0,5% [p/p]; n=10); grupo 2 (hipercolesterolémico + irbesartán 10 mg/kg/día; n = 10), y grupo 3 (hipercolesterolémico + losartán 10 mg/kg/día; n = 10). Los animales se mantuvieron en este régimen durante 18 semanas

Resultados

Tras 18 semanas de tratamiento los valores de colesterol total (CT) y lipoproteínas de baja densidad (LDL) en los grupos tratados con irbesartán y losartán fueron significativamente menores que en el grupo 1 (a = 0,05; p < 0,05 y p < 0,01, respectivamente). Además, los valoresde lipoproteínas de alta densidad (HDL) fueron mayores en los grupos tratados que en el hipercolesterolémico (a = 0,05; p < 0,05 y p < 0,01, respectivamente) cuando consideramos la misma concentración de colesterol total en los grupos tratados y en el hipercolesterolémico. A pesar del efecto de los fármacos sobre los parámetros mencionados anteriormente, el tratamiento con irbesartán o losartán no mejoró la relajación dependiente ni independiente del endotelio en los anillos de las arterias aorta y mesentérica. El tratamiento con irbesartán y losartán disminuyó la contracción inducida por NA en anillos de aorta, con respecto al grupo hipercolesterolémico (a = 0,05; p < 0,05). También se comprobó que el tratamiento con irbesartán mejoraba el incremento de la contracción inducida por serotonina en las arterias coronarias proximales con respecto al grupo hipercolesterolémico (a = 0,05; p < 0,001)

Conclusiones

Estos resultados indican que irbesartán y losartán restauran la contracción inducida por NA en arterias aisladas de conejo hipercolesterolémico y mejoran el perfil lipídico en conejos alimentados con una dieta rica en colesterol

Resumen
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

Palabras clave
Irbesartán, Losartán, Antagonista del receptor de angiotensina II, Conejos alimentados con dieta rica en colesterol, Arterias (aorta coronaria mesentérica [quinta rama])
Key words
Irbesartan, Losartan, Angiotensin II receptor antagonist, Cholesterol-fed rabbit, Arteries (aorta coronary mesenteric [5th branch])
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Correspondencia: Departamento de Farmacología. Facultad de Medicina.Universidad Complutense. 28040 Madrid
Copyright © 2002. Sociedad Española de Arteriosclerosis y Elsevier España, S.L.