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The influence of angiotensin-converting enzyme inhibitors on the aorta elastin metabolism in diet-induced hypercholesterolaemia in rabbits

Department of Experimental and Clinical Biochemistry Silesian Medical Academy, Katowice, Poland, wojwoj{at}mp.pl, First Clinic of Internal Medicine Silesian Medical Academy, Katowice, Poland

Jan Gminski

Department of Experimental and Clinical Biochemistry Silesian Medical Academy, Katowice, Poland, First Clinic of Internal Medicine Silesian Medical Academy, Katowice, Poland

Krzysztof Siemianowicz

Department of Experimental and Clinical Biochemistry Silesian Medical Academy, Katowice, Poland, First Clinic of Internal Medicine Silesian Medical Academy, Katowice, Poland

Malgorzata Goss

Department of Experimental and Clinical Biochemistry Silesian Medical Academy, Katowice, Poland

Marek Machalski

First Clinic of Internal Medicine Silesian Medical Academy, Katowice, Poland

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.

Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 1, 37-42 (2001)
DOI: 10.3317/jraas.2001.006


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