EFFECTS OF MANIPULATION OF DIETARY-CHOLESTEROL ON THE FUNCTION OF THETHORACIC AORTA FROM NEW-ZEALAND WHITE-RABBITS

Animal studies, while generally showing loss of endothelium-dependent responses after an elevation in plasma cholesterol, have provided conf licting reports with regard to recovery of function after normalisatio n of cholesterol level. Therefore, we assessed changes in vascular fun ction after a period of hypercholesterolaemia and the subsequent effec t of normalisation of cholesterol levels. Contractile responses to phe nylephrine (PE) and endothelium-dependent relaxation in response to ca rbachol 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% c holesterol diet for 20 weeks, followed by standard diet for 20 more we eks, and from their respective age-matched controls. Cholesterol level s 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 standa rd 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 peri od of hypercholesterolaemia (E(max) 69 +/- 9%; 95 +/- 3% age-matched c ontrol); the effect was reversed after reintroduction of standard diet (E(max) 79 +/- 6%; 82 +/- 2% age-matched control). Our results demons trate that endothelium-dependent relaxation is impaired after a long-t erm 0.3% cholesterol diet. Furthermore, after reintroduction of a norm al diet, there is no further impairment of endothelium-dependent relax ation and endothelium function improves.