Effects of chronic ET receptor antagonism on endothelium-dependent relaxation in control Wistar (A) and diabetic GK (B) rats. ETA receptor blockade restored maximum ACh induced relaxation in GK basilar arteries to greater than control values. While high dose blockade caused paradoxical vasoconstriction in diabetic animals, it improved the dilatory response in control rats. Results are shown as mean ± SEM, *p<0.001 repeated measures of ANOVA. Significant posthoc comparisons (P<0.05) for control Wistar groups are vehicle vs LD, vehicle vs HD, atrasentan vs LD, atrasentan vs HD and LD vs HD. For GK groups, vehicle vs atrasentan, atrasentan vs LD, and atrasentan vs HD were significantly different.