This study examined the effects of dietary supplementation with
cod-liver oil on impaired endothelium-dependent relaxations in
hypercholesterolemia and in
atherosclerosis in porcine coronary arteries. Sixteen male Yorkshire pigs underwent balloon endothelium removal of the left coronary arteries and were fed a 2% high-
cholesterol diet for 10 weeks, with or without dietary supplementation of
cod-liver oil (30 ml/day) (oil-fed and
cholesterol-fed groups, respectively). This model allowed the simultaneous examination of the effects of dietary
cod-liver oil on vascular reactivity in
hypercholesterolemia alone (right coronary artery) and in
atherosclerosis (left coronary artery). After 10 weeks of feeding, the dietary treatment with
cod-liver oil caused an increase in plasma levels of
eicosapentaenoic acid and a decrease in the plasma levels of
arachidonic acid, whereas the treatment had no significant effect on the increases in plasma
lipid levels induced by the high-
cholesterol feeding. Morphometric analysis showed significant inhibition of
coronary atherosclerosis by the treatment. Endothelium-dependent responses were examined in vitro in ring preparations and in bioassay experiments. Endothelium-dependent relaxations to
bradykinin,
serotonin, and
adenosine 5'-diphosphate were larger in both right and left coronary arteries from oil-fed than from
cholesterol-fed animals. Aggregating platelets from
cholesterol-fed and oil-fed pigs induced comparable, larger endothelium-dependent relaxations in rings from oil-fed than from
cholesterol-fed pigs. The contractions induced by
serotonin or aggregating platelets were significantly inhibited in rings with endothelium from oil-fed pigs, whereas they were comparable in rings without endothelium in both groups. Relaxations to
sodium nitroprusside and contractions to
potassium chloride or
serotonin were comparable in rings without endothelium in both groups. The bioassay experiments revealed that the release of
endothelium-derived relaxing factor in response to
bradykinin and the relaxations of vascular smooth muscle to the endothelial factor were greater after the
fish-oil diet. These results indicate that dietary supplementation of
cod-liver oil delays the impairment of endothelium-dependent relaxations in
hypercholesterolemia and in
atherosclerosis, partly because of an improved release of
endothelium-derived relaxing factor and partly because of an improved relaxation of coronary smooth muscle to the factor.