title: Reciprocal regulation of cholesterol excretion in apolipoprotein E-null mice by angiotensin II type 1 and type 2 receptor deficiency.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime, Japan.
authors: Masaru
authors: M
authors: Iwai
authors: Hisako
authors: H
authors: Sone
authors: Harumi
authors: H
authors: Kanno
authors: Tomozo
authors: T
authors: Moritani
authors: Masatsugu
authors: M
authors: Horiuchi
mesh_terms: D000214:Acyl Coenzyme A / Q000096:biosynthesis; D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency* / Q000235:genetics; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology*; D001646:Bile / Q000737:chemistry; D001713:Biphenyl Compounds / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D005243:Feces / Q000737:chemistry; D000077405:Irbesartan; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D044139:Receptor, Angiotensin, Type 2 / Q000172:deficiency* / Q000235:genetics; D011973:Receptors, LDL / Q000096:biosynthesis; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D000214:Acyl Coenzyme A; D048868:Adaptor Proteins, Signal Transducing; C119712:Agtrap protein, mouse; D047228:Angiotensin II Type 1 Receptor Blockers; D001057:Apolipoproteins E; D001713:Biphenyl Compounds; D002791:Cholesterol, Dietary; D044139:Receptor, Angiotensin, Type 2; D011973:Receptors, LDL; D013777:Tetrazoles; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D002784:Cholesterol; D000077405:Irbesartan