HBPRCA Astra Award. Therapeutic restoration of endothelial function in hypercholesterolaemic subjects: effect of fish...

1. Endothelial dysfunction, evidenced as an impaired response to acetylcholine, is well documented in hypercholesterolaemic subjects. We examined the ability of dietary supplementation with fish oils to restore endothelial function in forearm resistance vessels in these patients and compared this with restoration by lipid-lowering therapy. 2. Responses of forearm blood flow to acetylcholine (4.6, 9.25, 18.5 and 37 micrograms/min) and sodium nitroprusside (200, 400, 800 and 1600 ng/min) were obtained using forearm venous occlusion plethysmography in nine hypercholesterolaemic and seven age-matched control subjects. The dose-response curve to acetylcholine was significantly blunted in hypercholesterolaemic subjects when compared with controls (P < 0.001). Responses to sodium nitroprusside were not different between the two groups (P = 0.37). 3. Lipid-lowering therapy decreased total plasma cholesterol levels by 33% and significantly augmented the responses to acetylcholine (P = 0.001) but not to sodium nitroprusside in the hypercholesterolaemic subjects. 4. Dietary supplementation with fish oils had no effect on either total or low density lipoprotein-cholesterol but significantly augmented the responses to acetylcholine (P = 0.011) in hypercholesterolaemic subjects. Responses to sodium nitroprusside were not altered (P = 0.94). 5. This study shows that endothelium-dependent relaxation is impaired in subjects with high cholesterol levels and that this impairment can be reversed by lowering low density lipoproteins (LDL) cholesterol levels. In addition, we demonstrate that restoration of endothelial function can occur without changes in LDL levels, by dietary supplementation with fish oils.