EFFECTS OF VITAMIN-E ON ENDOTHELIUM-DEPENDENT CORONARY FLOW IN HYPERCHOLESTEROLEMIC DOGS

The authors studied the effect of vitamin E on endothelium-dependent c oronary flow in hypercholesterolemic dogs. Adult mongrel dogs weighing 7.4 +/- 1.0 kg were divided into control, hypercholesterolemic and vi tamin E groups. The animals in the hypercholesterolemic group were fed a diet enriched with cholesterol (5% w/w) and coconut oil (10% w/w) f or 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 chole sterol levels were evaluated at the beginning and at the end of the ex periment using a commercial enzyme kit and a Beckman analyzer. The cor onary flow was determined by electromagnetic flowmetry using a probe p ositioned in the left anterior descending coronary artery, near the os tium. A needle connected to a perfusion pump was introduced into the c oronary artery for the administration of acetylcholine and sodium nitr oprusside at a rate of 5 mu g/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 co ntent and malonic dialdehyde (MDA) were also measured in isolated coro nary vessel specimens. At the end of 40 days, the serum cholesterol le vels had increased by 226% and 190% in the hypercholesterolemic and vi tamin E groups, respectively. However, the difference in the levels of these two groups was not significant (P > 0.05). The aortic blood pre ssure and heart rate remained unchanged during acetylcholine administr ation. In contrast, systolic and diastolic pressure fell and the heart rate increased during the infusion of sodium nitroprusside, The tissu e 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 chol esterol treated animals (P < 0.05). The percent change in coronary flo w during acetylcholine administration was significantly lower in the h ypercholesterolemic group when compared with control animals (P < 0.05 ) but was unaltered in the vitamin E group (P > 0.05). During sodium n itroprusside administration, the coronary flow increased in the vitami n E group (P < 0.05). The authors conclude that hypercholesterolemia r educes endothelium-dependent coronary flow and increases the tissue ch olesterol content and MDA of coronary arteries. Vitamin E decreases th e MDA and the tissue cholesterol content without significantly affecti ng the total serum cholesterol level. Vitamin E may thus restore coron ary flow by reverting endothelial dysfunction.