Reciprocal regulation of cholesterol excretion in apolipoprotein E-null mice by angiotensin II type 1 and type 2 receptor deficiency
2013
Iwai, Masaru | Sone, Hisako | Kanno, Harumi | Moritani, Tomozo | Horiuchi, Masatsugu
AIMS: The effects of AT₁ and AT₂ receptor deficiency on the intake and excretion of cholesterol were examined using atherosclerotic apolipoprotein E-null (ApoEKO) mice. MAIN METHODS: ApoEKO, AT₁a/ApoEKO and AT₂/ApoEKO mice received a high-cholesterol diet (HCD: 1.25% cholesterol) for 10days before sampling. KEY FINDINGS: Plasma total cholesterol level was lower in AT₁a/ApoEKO mice and higher in AT₂/ApoEKO mice than in ApoEKO mice with a high cholesterol intake. In these mice, cholesterol content in feces was higher in AT₁a/ApoEKO mice and lower in AT₂/ApoEKO mice than in ApoEKO mice. Moreover, cholesterol content in bile tended to be higher in AT₁a/ApoEKO mice and lower in AT₂/ApoEKO mice than in ApoEKO mice, while a significant difference was observed only between AT₁a/ApoEKO and AT₂/ApoEKO mice. Cholesterol content and expression of HMG-CoA reductase and LDL receptor in liver were not different among the groups. Similar but weaker changes were also observed with a normal standard diet. Treatment with an AT₁ receptor blocker, irbesartan, increased cholesterol content in bile and tended to increase cholesterol excretion into feces in ApoEKO mice with HCD. SIGNIFICANCE: These results suggest that AT₁ and AT₂ receptor stimulation was involved in the regulation of cholesterol excretion into bile and feces, and that the regulation acted reciprocally in a cholesterol overload condition with HCD.
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