1.
Cholesterol feeding of rabbits impairs the endothelium-dependent relaxation (EDR) evoked by
acetylcholine (ACh) in the aorta. The experiments described in this paper were undertaken to examine the influence of age upon this phenomenon. 2. Rabbits aged 8 weeks and 46 weeks were fed a diet containing 2%
cholesterol and other
lipids for 4 weeks. Age-matched control animals were fed a standard rabbit diet. The concentrations of
cholesterol and
triglycerides in plasma were measured and the extent of
atherosclerosis was estimated by staining the aortae with
Sudan Red. Light and electron microscopy were undertaken also. 3. Rings of aorta were prepared for recording isometric tension. They were contracted with
noradrenaline (NA) and EDR elicited by adding ACh. 4. The young rabbits showed
weight gain, hypercholesterolaemia, prominent
Sudan Red staining, together with scanning and transmission electron microscopic (SEM and TEM) features of
cholesterol-induced
atherosclerosis. The older animals showed significant
weight loss and hypercholesterolaemia. The aortae of these animals showed no significant sudanophilia or light microscopic features of
atherosclerosis. The SEM appearances were similar to the young animals fed
cholesterol. 5. EDR to ACh was significantly impaired in both groups of
cholesterol-fed rabbits. The maximal relaxations to ACh in young control and
cholesterol-fed rabbits were 46.4 +/- 2.9% and 24.0 +/- 4.3% (mean +/- s.e. mean, n = 8, P less than 0.05) of the contractile response to NA (1 mumol 1(-1]. The corresponding results in the age control and
cholesterol-fed rabbits were 31.8 +/- 3.9% and 9.1 +/- 1.5% (n = 9, P less than 0.05). 6. The young rabbits were far more susceptible to
cholesterol-induced
atherosclerosis than older animals and these changes were accompanied by loss of EDR. In the older animals and these changes were accompanied by loss of EDR. In the older animals the loss of the latter property was not accompanied by a significant degree of
atherosclerosis although hypercholesterolaemia was present.