The influence of angiotensin-converting enzyme inhibitors on the aorta elastin metabolism in diet-induced hypercholesterolaemia in rabbits.
Aortic elastin turnover is significantly accelerated in atherosclerosis, partly because of activation of the renin-angiotensin-aldosterone system caused by hypercholesterolaemia. We postulated that angiotensin-converting enzyme inhibitors (ACE-I) prevent the aortic elastin loss in experimental hypercholesterolaemia. Two doses of ACE-I (captopril, enalapril and quinapril) were used: a dose equivalent to that applied to human subjects and a dose 10 times higher. We found that the increase in serum and aortic elastolytic activity in cholesterol-fed rabbits was prevented by high-dose captopril. The elastin content in aorta homogenates from cholesterol-fed rabbits was significantly decreased. The higher dose of captopril, but no other ACE-I, prevented this decrease in aortic elastin content. In cholesterol-fed rabbits the elastin-bound calcium content was significantly elevated. The higher doses of captopril and enalapril lowered the elastin-bound calcium content. In serum and aortic homogenates of cholesterol-fed rabbits, ACE activity was elevated by 15% and 77%, respectively. Both doses of captopril, enalapril and quinapril prevented this cholesterol-induced increase in serum and aortic ACE activity. We conclude that: 1) administration of captopril at doses 10 times higher than those used in humans prevents hypercholesterolaemia increased aortic elastin loss. 2) higher doses of captopril and enalapril prevent the hypercholesterolaemia-induced increase in aortic elastin-bound calcium.
Wojakowski
W
W
Department of Experimental and Clinical Biochemistry, Silesian Medical Academy, Katowice, Poland. wojwoj@mp.pl
Gminski
J
J
Siemianowicz
K
K
Goss
M
M
Machalski
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002216:Captopril / Q000494:pharmacology; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004549:Elastin / Q000378:metabolism*; D004656:Enalapril / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000209:etiology* / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D000077583:Quinapril; D011817:Rabbits; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D002791:Cholesterol, Dietary; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D004656:Enalapril; D004549:Elastin; D002216:Captopril; D000077583:Quinapril; D002118:Calcium