Circulation, Vol 78, 1421-1430, Copyright © 1988 by American Heart Association
H Shimokawa and PM Vanhoutte
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.
ARTICLES
Dietary cod-liver oil improves endothelium-dependent responses in hypercholesterolemic and atherosclerotic porcine coronary arteries
Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota 55905.
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