Segmental impairment of endothelium-mediated relaxation in thoracic aortas from atherosclerotic rabbits. Comparison to cholesterol infiltration and energy metabolism.

Three sets of parameters, (i) relaxation to acetylcholine (Ach), ATP and NaNO2, (ii) cholesterol content in aortic tissue, and (iii) energy metabolism were compared in normal and atherosclerotic rabbits, fed 1% cholesterol for eight weeks. A special protocol was envisaged to permit a strict comparison between Ach, ATP and NaN O2 at different levels of thoracic aorta, in each rabbit. A gradual impairment of the endothelium-dependent relaxation to Ach and ATP was found at different levels of the thoracic aorta from hypercholesteromic rabbits. By contrast, NaNO2--endothelium-independent--maintained its relaxing power quite normally at all aortic levels. A close correlation was evident between the impairment of aorta relaxation to Ach and the cholesterol infiltration in the vessel wall, being the correlation coefficient -0.85 (P less than 0.001). A correlation was also evident for ATP, but to a lower degree, being the correlation coefficient -0.61 (P less than 0.01). Energy metabolism and related parameters (ATP, ADP, AMP, adenosine, inosine, GTP, GDP, guanosine, NAD, NADP, total adenylate nucleotides and adenylate energy charge) were not modified by the cholesterol diet. These data show that the gradual impairment of endothelium-dependent relaxation, decreasing down the thoracic aorta of hypercholesterolemic rabbits, and correlated with cholesterol content in the aortic wall, may be considered as an index of a very early atherogenic damage, prior to variation in the parameters of energy metabolism and purine turnover.