Effects of vitamin E on endothelium-dependent coronary flow in hypercholesterolemic dogs

Abstract

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.

Vitamin E Modulation of Cardiovascular Disease

“…In this regard, FMD has been used to examine the effect of dietary antioxidants on endothelial function. Although vitamin E supplementation in hypercholesterolemic animal models has been shown to be effective in preserving endothelial vasodilator function,25 the effect of vitamin E supplementation on FMD in humans has been equivocal 38‐41. However, when vitamin E is consumed with vitamin C, it appears to be effective in reducing FMD.…”

“…Although vitamin E supplementation in hypercholesterolemic animal models has been shown to be effective in preserving endothelial vasodilator function, 25 the effect of vitamin E supplementation on FMD in humans has been equivocal. [38][39][40][41] However, when vitamin E is consumed with vitamin C, it appears to be effective in reducing FMD. For example, when vitamin E (800 IU/day) was included with vitamin C (2 g/ day) supplementation, it further increased the improvement of FMD in chronic smokers.…”

Vitamin E: Focus on Microcirculation

“…Of more immediate interest is the observation that hypercholesterolemia impairs endotheliumdependent vasorelaxation in both macro-and microvascular networks and that this effect is normalized by vitamin E (3,40,67). Vitamin E was found to preserve endothelium-dependent vasorelaxation in the coronary arteries of hypercholesterolemic dogs (62), and in ear microvessels of rabbits (89). Further effects of vitamin E in experimental hypercholester- olemia with immediate consequences for the microcirculation system are the normalization of suppressed prostacyclin production in rabbit arteries (117) and of increased endothelial cell permeability to plasma proteins and other macromolecules in guinea pigs (101).…”

Efeito da berinjela sobre os lípides plasmáticos, a peroxidação lipídica e a reversão da disfunção endotelial na hipercolesterolemia experimental

“…Os mecanismos envolvidos na redução dos eventos e na mortalidade por doença coronária, quando ocorre diminuição do colesterol plasmático, parecem estar relacionados à reversão da disfunção endotelial e estabilização da placa de aterosclerose, uma vez que não se observa aumento significante do diâmetro vascular ao nível da placa de aterosclerose 4 . Mais recentemente, tem-se verificado que as substân-cias anti-oxidantes são capazes de reverter a disfunção endotelial provocada pela hipercolesterolemia 8,9 e também reduzir o numero de eventos coronários 10 , embora sua utilização, na prática médica, careça, ainda, de informação mais conclusivas.…”