Influences of hypercholesterolemia on the vessel function of isolated rat thoracic aorta]

Mature male rats (SD strain, 8-week-old) were fed with a normal diet or a high cholesterol diet (HC: 1.5% cholesterol and 0.5% Na cholate in the normal diet) up to 8 weeks, and we examined how the vascular function level of the isolated thoracic aorta and the histological figures of some tissues including the aorta would change. 1) The contracting reactivity to phenylephrine (Phe, 10 microM) and the relaxing reactivity to acetylcholine (1 microM) measured thereafter remained unchanged during the period of aging and were not influenced by HC-feeding. The addition of L-arginine (Arg, 100 microM) did not affect the results. 2) The ability of the aorta to release NO and to relax, which was evaluated as the extent of the endothelium-dependent potentiation by NG-monomethyl-L-arginine (NMA) of the Phe contraction, did not change by HC-feeding up to 4 weeks, but appears to be attenuated after 8-week feeding. 3) The EC50 of NMA for the potentiation estimated without the addition of Arg remained unchanged, while the one in the presence of Arg gradually increased with aging but not with HC-feeding. 4) The histopathological study of the aorta and other tissues failed to detect any notable atherogenic changes in any of the HC-fed groups. The results indicate that under the experimental conditions employed, HC-feeding would not develop any significant atherogenic histopathological changes in the endothelium-smooth muscle preparation, but may induce some dysfunction in the NO-release mediated and auto-regulatory function of the vascular tone.