The effects of renin-angiotensin system inhibition on aortic cholesterol content in cholesterol-fed rabbits.
To investigate how the renin-angiotensin system (RAS) might be involved in cholesterol-induced atherosclerosis, we studied the effects of a nonsulhydryl angiotensin converting enzyme (ACE) inhibitor, enalapril, and an angiotensin II receptor antagonist, E-4177, in cholesterol fed rabbits. Japanese white rabbits were randomly divided into four groups with the following dietary regimens: group A (n = 8) received a standard diet; group B (n = 8) had a 0.5% cholesterol diet; group C (n = 8) had a 0.5% cholesterol diet plus enalapril (10 mg/kg/day, p.o.); group D (n = 8) received a 0.5% cholesterol diet plus E-4177 (20 mg/kg/day, p.o.) and were fed these diets for 5 weeks. Enalapril or E-4177 had no significant effect on either the total plasma or the high density lipoprotein (HDL) cholesterol concentrations. However, the aortic cholesterol content in groups C and D was equally significantly less than that in group B. The plasma and aortic ACE activities were significantly reduced only in group C compared with those in the other groups. The aortic ACE mRNA and AT1 mRNA levels were assessed by a reverse transcription polymerase chain reaction (RT-PCR). The aortic ACE mRNA level was only significantly less in group C than in any of the other groups. The aortic AT1 mRNA level increased significantly in group B compared with that in group A and was significantly and equally reduced in both groups C and D compared with that in group B. These data indicate that angiotensin II rather than ACE may therefore be related to aortic cholesterol content. It follows therefore that the inhibition of angiotensin II by either ACE inhibitor or angiotensin II (type 1) receptor antagonist may play a role in prevention of atherosclerosis.
Sugano
M
M
Department of Bioclimatology and Medicine, Medical Institute of Bioregulation, Kyushu University, Japan.
Makino
N
N
Yanaga
T
T
D000804:Angiotensin II / Q000235:genetics / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001161:Arteriosclerosis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D002455:Cell Division; D002784:Cholesterol / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D002851:Chromatography, High Pressure Liquid; D004656:Enalapril / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008074:Lipoproteins / Q000378:metabolism; D015345:Oligonucleotide Probes / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D011897:Random Allocation; D011945:Receptors, Angiotensin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013053:Spectrophotometry
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002791:Cholesterol, Dietary; D007093:Imidazoles; D008074:Lipoproteins; D015345:Oligonucleotide Probes; D011725:Pyridines; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C083778:3-((2'-carboxybiphenyl-4-yl)methyl)-2-cyclopropyl-7-methyl-3H-imidazo(4,5-b)pyridine; D004656:Enalapril; D002784:Cholesterol