Vascular angiotensin-converting enzyme activity in cholesterol-fed rabbits: effects of enalapril.
Many reports have shown inhibitory effects of angiotensin-converting enzyme (ACE) inhibitors on the progression of atherosclerotic plaque lesions in vascular tissue of experimental models. However, no report has shown alterations of ACE activity in vascular tissue during the process of atherosclerosis. We measured ACE activity in plasma and aortic tissue in rabbits fed a cholesterol-rich (1%) or normal diet for 10 weeks. We also evaluated the blood pressure response to angiotensin (Ang) I and II. These data were compared in untreated rabbits and in rabbits receiving chronic treatment with an ACE inhibitor, enalapril (3 mg/kg/day for 10 weeks). ACE activity in aortic tissue, but not in plasma, in cholesterol-fed rabbits was gradually but significantly increased compared with that in noncholesterol-fed rabbits even after the 4-week feeding period, when no atherosclerotic lesion was observed in the aortic tissue. Treatment with enalapril for 10 weeks, but not 4 weeks, significantly reduced the ACE activity in aortic tissue in association with the reductions in the elevated Ang II level and the atherosclerotic plaque area of the aortic tissue. These results indicated that ACE activity in aortic tissue was increased during the early phase of atherosclerotic process.
Hoshida
S
S
First Department of Medicine, Osaka University School of Medicine, Suita, Japan.
Nishida
M
M
Yamashita
N
N
Igarashi
J
J
Aoki
K
K
Hori
M
M
Kuzuya
T
T
Tada
M
M
D000803:Angiotensin I / Q000097:blood / Q000494:pharmacology; D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000201:enzymology* / Q000473:pathology; D001161:Arteriosclerosis / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D001794:Blood Pressure / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D004656:Enalapril / Q000494:pharmacology*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism*; D011817:Rabbits
D000806:Angiotensin-Converting Enzyme Inhibitors; D002791:Cholesterol, Dietary; D000804:Angiotensin II; D004656:Enalapril; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A