title: Effect of captopril on serum lipid levels and cardiac mitochondrial oxygen consumption in experimentally-induced hypercholesterolemia in rabbits.
abstract: Angiotensin converting enzyme inhibitors are widely used in therapy of cardiovascular diseases. However, the consensus on effects of these inhibitors in control of myocardial oxygen consumption during the process of experimental hypercholesterolemia and under the condition of endothelial dysfunction has not been reached. Here we examined effects of captopril, an angiotensin converting enzyme inhibitor, on serum lipid levels and oxygen consumption rate in mitochondria isolated from heart of rabbits treated by hypercholesterolemic diet. During the twelve-week period, the Chinchilla male rabbits were daily treated by saline (controls); 1 % cholesterol diet; 5 mg/kg/day captopril or 1 % cholesterol + 5 mg/kg/day captopril. Total- and high-density lipoprotein cholesterol and triglyceride in serum were measured spectrophotometrically. The left ventricle mitochondrial fraction was isolated and myocardial oxygen consumption was measured by Biological Oxygen Monitor. Mitochondria isolated from hearts of rabbits exposed to hypercholesterolemic diet showed significantly reduced respiration rates (state 3 and state 4) with altering adenosine diphosphate/oxygen ratio, whereas the respiratory control ratio was not affected when compared to controls. Mitochondria from cholesterol/captopril-treated animals showed significantly reduced respiration rates without altering adenosine diphosphate/oxygen ratio index or respiratory control ratio. Although captopril did not exert the favorable effect on serum lipid levels in cholesterol-treated animals, it restored the mitochondrial oxygen consumption. Further studies should be performed to define the underlying physiological and/or pathophysiological mechanisms and clinical implications.
authors.affiliation: Institute of Physiology, School of Medicine, University of Belgrade, Belgrade, Serbia. zvezdanak@med.bg.ac.rs
authors.forename: Z
authors.initials: Z
authors.lastname: Kojic
authors.forename: K
authors.initials: K
authors.lastname: Gopcevic
authors.forename: D
authors.initials: D
authors.lastname: Marinkovic
authors.forename: G
authors.initials: G
authors.lastname: Tasic
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002216:Captopril / Q000494:pharmacology*; D019069:Cell Respiration / Q000187:drug effects; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008055:Lipids / Q000097:blood*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D011817:Rabbits; D013053:Spectrophotometry; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D008055:Lipids; D000244:Adenosine Diphosphate; D002216:Captopril; D010100:Oxygen