Differences in onset of impaired endothelial responses and in effects of vitamin E in the hypercholesterolemic rabbit carotid and renal arteries.

Hypercholesterolemia (HC) is known to be associated with impaired endothelium-mediated responses in the vasculature. Evidence suggests that increased levels of reactive oxygen species (ROS) in the vessel wall may contribute to the impairment by decreasing the biological activity of endothelium-derived relaxing factor (EDRF). We compared the relative onset of HC-induced impairment of endothelial responses in the carotid and renal arteries and investigated the potentially beneficial effect of the antioxidant vitamin E. Rabbits were fed a 1% cholesterol-enriched diet for 4 and 8 weeks, and vascular responses were compared using isolated ring segments of the carotid and renal arteries. In the carotid artery, relaxant responses to acetylcholine (ACh) were significantly and progressively impaired after 4 and 8 weeks; in the renal artery, however, responses were only slightly impaired after 8 weeks. There were no changes in responsiveness to A23187 or sodium nitroprusside (SNP) in either artery. We tested the effect of 0.2% vitamin E by adding it to the diet for 4 weeks, after an initial 4-week of feeding of 1% cholesterol alone. Vitamin E reversed impaired responses to ACh in the carotid but not the renal artery and also enhanced relaxant responses to A23187. We conclude that the carotid artery is more susceptible than the renal artery to HC-induced endothelial impairment and that ROS may play a role in this impairment in the carotid artery but not in the renal artery.