DIFFERENCES IN ONSET OF IMPAIRED ENDOTHELIAL RESPONSES AND IN EFFECTSOF VITAMIN-E IN THE HYPERCHOLESTEROLEMIC RABBIT CAROTID AND RENAL-ARTERIES

Hypercholesterolemia (HC) is known to be associated with impaired endo thelium-mediated responses in the vasculature. Evidence suggests that increased levels of reactive oxygen species (ROS) in the vessel wall m ay contribute to the impairment by decreasing the biological activity of endothelium-derived relaxing factor (EDRF). We compared the relativ e onset of HC-induced impairment of endothelial responses in the carot id and renal arteries and investigated the potentially beneficial effe ct of the antioxidant vitamin E. Rabbits were fed a 1% cholesterol-enr iched diet for 4 and 8 weeks, and vascular responses were compared usi ng isolated ring segments of the carotid and renal arteries. In the ca rotid artery, relaxant responses to acetylcholine (ACh) were significa ntly and progressively impaired after 4 and 8 weeks; in the renal arte ry, however, responses were only slightly impaired after 8 weeks. Ther e were no changes in responsiveness to A23187 or sodium nitroprusside (SNP) in either artery, We tested the effect of 0.2% vitamin E by addi ng 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 t he carotid but not the renal artery and also enhanced relaxant respons es to A23187. We conclude that the carotid artery is more susceptible than the renal artery to HC-induced endothelial impairment and that RO S may play a role in this impairment in the carotid artery but not in the renal artery.