Hypercholesterolaemia severely impairs EDRF-dependent collateral perfusion following acute arterial occlusion in...

1. We have used a rabbit isolated buffer-perfused ear as a model of acute arterial occlusion to investigate the effects of dietary-induced hypercholesterolaemia on EDRF-dependent collateral perfusion. The effects of hypercholesterolaemia on endothelium-dependent relaxations to acetylcholine were also investigated in the unligated isolated buffer-perfused ear of the rabbit. 2. In rabbits receiving a high cholesterol diet (1%) for 4 weeks, blood cholesterol levels were significantly (P < 0.001) increased (26.0 +/- 3.6 vs. 2.6 +/- 0.6 mmol l-1), EDRF-dependent collateral perfusion was similar to that in age-matched controls for the first 15 min after occlusion but then decreased and was significantly (P < 0.01) less than control during the maintenance phase of collateral perfusion. 3. Cholesterol feeding for 8 weeks (blood cholesterol = 56.2 +/- 3.8 vs. 1.3 +/- 0.1 mmol l-1) was associated with almost complete impairment of collateral perfusion, an effect previously observed following inhibition of EDRF synthesis. 4. Endothelium-dependent relaxations to acetylcholine in isolated perfused ears were impaired in the rabbits fed the diet for 8 weeks but not those fed for 4 weeks. In the 8 week group, the maximum relaxation of tone was 32.6 +/- 11.6% and was significantly (P < 0.01) less than that in the controls (77.9 +/- 5.7%). 5. We conclude that EDRF-dependent collateral perfusion is severely impaired in hypercholesterolaemia and that the level of impairment is related to the duration of feeding.