Altered vascular reactivity in the rabbit during hypercholesterolemia

Rabbits were fed a 0.6% cholesterol diet (HC) for 4, 6 or 8 weeks. Age- and sex-matched controls (C) were fed rabbit chow. Isometric contractions with cumulative doses of norepinephrine (NE), histamine (HIS) and serotonin (5-HT) were measured in isolated aortic rings. Serum cholesterol levels in female HC animals increased approximately 19, 20 and 25 times control values, and male HC animals increased approximately 17, 20 and 18 times control values after 4, 6 and 8 weeks, respectively. In the present study, altered vascular responsiveness during hypercholesterolemia was demonstrated in isolated vessels with major changes occurring after 4 weeks. Female HC rabbits exhibited increased maximal responses to all agents tested and were greater than male HC rabbits. Male HC rabbits had increased maximal responses to NE and HIS but not 5-HT. Significant changes were also observed in both male and female HC animals at 6 and 8 weeks, however these were somewhat attenuated when compared to 4-week HC animals. These results suggest that changes in vascular responsiveness due to hypercholesterolemia can be demonstrated very early after the onset of hypercholesterolemia and can be demonstrated in isolated vessels bathed in cholesterol-free media.