The effect of atherosclerosis on endothelium-dependent relaxation in the aorta and intracranial arteries of rabbits.

The effect of hypercholesterolemia on vascular responsiveness was studied in isolated rabbit arteries. The arteries of animals maintained on a cholesterol-rich (1%) diet for 6 months had more pronounced intimal lesion than those receiving the diet for 3 months. The aortas were more severely damaged than the carotid or basilar arteries. Segments of the arteries were mounted in organ chambers for isometric tension recording or for measurement of the endothelium-derived relaxing factor. Endothelium-independent relaxation induced by glyceryl trinitrate was not affected even in the most severely damaged arteries; endothelium-dependent relaxation in response to acetylcholine (ACh) and A23187 was progressively inhibited as the degree of fatty streak formation increased. In the carotid arteries, mean (+/- standard deviation) relaxation induced by 10(-5) M of ACh (expressed as a percentage of the maximum relaxation induced by 10(-4) M of papaverine) decreased from 87.33% +/- 6.30% in control tissues to 60.90% +/- 4.64% in vessels from animals subjected to 6 months of hypercholesterolemia (p less than 0.01); in the aortas, mean relaxation due to 10(-5) M of ACh was 85.08% +/- 8.03% in control tissues and 41.35% +/- 13.68% in hypercholesterolemic tissues (p less than 0.01). In the carotid arteries, mean relaxation induced by 10(-7) M of A23187 decreased from 95.81% +/- 3.58% in control tissues to 55.95% +/- 2.81% in hypercholesterolemic tissues (p less than 0.01); in the aortas, relaxation in response to 10(-7) M of A23187 was 73.73% +/- 4.35% in control tissues and 29.35% +/- 6.77% in hypercholesterolemic tissues (p less than 0.01). Intimal lesions were not produced in the basilar arteries even in rabbits with 12 months of hypercholesterolemia, and endothelium-dependent relaxation was preserved.