Alterations of vascular alpha 1-adrenergic contractile responses in hypercholesterolemic rabbit common carotid...

In rabbits fed a diet containing 1% cholesterol and 4% lard for 4 or 8 weeks, vascular responses to alpha 1-adrenoceptor agonists, epinephrine (EPI), phenylephrine (PE), norepinephrine (NE), methoxamine (MO), and clonidine (CL) were examined in isolated common carotid arteries by the cannula-insertion method. The high cholesterol diet caused no microscopic evidence of atherosclerosis, and vasodilatory responses to ACh were well maintained, even in the 8-week group. Vasoconstrictions to EPI were augmented and those to NE, MO, and CL were progressively decreased, but that to PE was not influenced in 4- and 8-week-treated groups. These agonist-induced constrictions were readily inhibited by bunazosin and WB 4101, indicating that these result from alpha 1A-adrenoceptor activations. CL- and MO-induced constrictions were much more sensitive to WB 4101. Chlorethylclonidine (CEC) inhibited CL- and MO-induced constrictions, but not PE-induced, at relatively larger doses. We suggest that vasoconstrictivity to alpha-adrenoceptor agonists is altered by hypercholesterolemia without accompanying atherosclerotic changes and endothelial dysfunction, at the early stage of hypercholesterolemia, the sensitivity of alpha 1-adrenoceptors might be decreased at smooth muscle cell levels, and different changes in contractile reactivity to alpha 1-agonists after cholesterol feedings might be due to a decrease in alpha 1A-adrenoceptors.