Effects of vitamin E on endothelium-dependent coronary flow in hypercholesterolemic dogs.
The authors studied the effect of vitamin E on endothelium-dependent coronary flow in hypercholesterolemic dogs. Adult mongrel dogs weighing 7.4 +/- 1.0 kg were divided into control, hypercholesterolemic and vitamin E groups. The animals in the hypercholesterolemic group were fed a diet enriched with cholesterol (5% w/w) and coconut oil (10% w/w) for 40 days. The vitamin E group received the same diet plus 400 IU of vitamin E during the last 15 days of the experiment. Total serum cholesterol levels were evaluated at the beginning and at the end of the experiment using a commercial enzyme kit and a Beckman analyzer. The coronary flow was determined by electromagnetic flowmetry using a probe positioned in the left anterior descending coronary artery, near the ostium. A needle connected to a perfusion pump was introduced into the coronary artery for the administration of acetylcholine and sodium nitroprusside at a rate of 5 micrograms/kg per min. The aorta was cannulated for the measurement of arterial blood pressure via a pressure transducer coupled to a Siemens multi-channel recorder. The tissue cholesterol content and malonic dialdehyde (MDA) were also measured in isolated coronary vessel specimens. At the end of 40 days, the serum cholesterol levels had increased by 226% and 190% in the hypercholesterolemic and vitamin E groups, respectively. However, the difference in the levels of these two groups was not significant (P > 0.05). The aortic blood pressure and heart rate remained unchanged during acetylcholine administration. In contrast, systolic and diastolic pressure fell and the heart rate increased during the infusion of sodium nitroprusside. The tissue cholesterol content and MDA were significantly (P < 0.05) increased in coronary artery specimens from the hypercholesterolemic compared to control animals. Vitamin E was able to reduce these increases in cholesterol treated animals (P < 0.05). The percent change in coronary flow during acetylcholine administration was significantly lower in the hypercholesterolemic group when compared with control animals (P < 0.05) but was unaltered in the vitamin E group (P > 0.05). During sodium nitroprusside administration, the coronary flow increased in the vitamin E group (P < 0.05). The authors conclude that hypercholesterolemia reduces endothelium-dependent coronary flow and increases the tissue cholesterol content and MDA of coronary arteries. Vitamin E decreases the MDA and the tissue cholesterol content without significantly affecting the total serum cholesterol level. Vitamin E may thus restore coronary flow by reverting endothelial dysfunction.
Jorge
P A
PA
Department of Experimental Medicine, State University of Campinas, São Paulo, Brazil.
Osaki
M R
MR
de Almeida
E
E
Credídio Neto
L
L
Metze
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000032:analysis; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000737:chemistry / Q000187:drug effects; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000032:analysis; D009599:Nitroprusside / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology* / Q000627:therapeutic use
D000975:Antioxidants; D014810:Vitamin E; D009599:Nitroprusside; D008315:Malondialdehyde; D002784:Cholesterol; D000109:Acetylcholine