Effects of manipulation of dietary cholesterol on the function of the thoracic aorta from New Zealand white rabbits

Animal studies, while generally showing loss of endothelium-dependent responses after an elevation in plasma cholesterol, have provided conflicting reports with regard to recovery of function after normalisation of cholesterol level. Therefore, we assessed changes in vascular function after a period of hypercholesterolaemia and the subsequent effect of normalisation of cholesterol levels. Contractile responses to phenylephrine (PE) and endothelium-dependent relaxation in response to carbachol were examined in thoracic aorta from New Zealand White rabbits (NZW) fed a 0.3% cholesterol diet for 20 weeks, from NZW fed a 0.3% cholesterol diet for 20 weeks, followed by standard diet for 20 more weeks, and from their respective age-matched controls. Cholesterol levels were increased in rabbits receiving the 0.3% cholesterol diet (12.7 +/- 3.2 mM; 0.5 +/- 0.1 mM control) and returned to normal when standard diet was reintroduced (0.8 +/- 2.0 mM). Contractile responses were not affected by the period of hypercholesterolaemia. Carbachol-induced relaxation of a submaximal PE contraction was impaired after the period of hypercholesterolaemia (E(max) 69 +/- 9%; 95 +/- 3% age-matched control); the effect was reversed after reintroduction of standard diet (E(max) 79 +/- 6%; 82 +/- 2% age-matched control). Our results demonstrate that endothelium-dependent relaxation is impaired after a long-term 0.3% cholesterol diet. Furthermore, after reintroduction of a normal diet, there is no further impairment of endothelium-dependent relaxation and endothelium function improves.