The purpose of this study was to determine whether the generation of a
neointima, an early step in the development of
atherosclerosis, affects endothelium-dependent or -independent vasodilation. The
neointima was induced, within 7 days, by positioning a nonocclusive
silicone collar around one carotid artery in rabbits. After 1, 2, 7, or 14 days segments were cut from the collar-surrounded region of this artery as well as from the
sham-operated contralateral artery and were used for isometric tension recording or for bioassay of
nitric oxide (NO). The
acetylcholine-induced release of NO was significantly reduced at 7 days. The tension recordings suggested that this already occurred at the earliest stages of
neointima formation. Neither the capacity of the endothelial cells to form NO in response to the
calcium ionophore A23187 nor the capacity of the underlying smooth muscle cells to relax in response to sources of exogenous NO (3-morpholinosydnonimine and
nitroglycerin) was affected by the
neointima. Therefore, the impaired endothelium-dependent relaxations to
acetylcholine are presumably due to a defect at the level of the endothelial
muscarinic receptors. The presence of a fully developed
neointima did not alter the responsiveness to
isoproterenol and
forskolin but enhanced
prostacyclin-mediated responses (assessed by
iloprost and 13-
hydroxyoctadecadienoic acid). These results illustrate selective alterations of endothelial and smooth muscle cell function in intima generation before fatty streak formation.