Reciprocal regulation of cholesterol excretion in apolipoprotein E-null mice by angiotensin II type 1 and type 2 receptor deficiency.

Aims: The effects of AT(1) and AT(2) receptor deficiency on the intake and excretion of cholesterol were examined using atherosclerotic apolipoprotein E-null (ApoEKO) mice.
Main Methods: ApoEKO, AT(1)a/ApoEKO and AT(2)/ApoEKO mice received a high-cholesterol diet (HCD: 1.25% cholesterol) for 10 days before sampling.
Key Findings: Plasma total cholesterol level was lower in AT(1)a/ApoEKO mice and higher in AT(2)/ApoEKO mice than in ApoEKO mice with a high cholesterol intake. In these mice, cholesterol content in feces was higher in AT(1)a/ApoEKO mice and lower in AT(2)/ApoEKO mice than in ApoEKO mice. Moreover, cholesterol content in bile tended to be higher in AT(1)a/ApoEKO mice and lower in AT(2)/ApoEKO mice than in ApoEKO mice, while a significant difference was observed only between AT(1)a/ApoEKO and AT(2)/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 AT(1) 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 AT(1) and AT(2) 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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