Augmented adrenergic contractions of carotid arteries from cholesterol-fed rabbits due to endothelial cell dysfunction.

Transmural electrical stimulation was used to elicit frequency-dependent adrenergic neurogenic contractions in isolated carotid arteries from cholesterol-fed and control rabbits. In rings with endothelium, responses to adrenergic nerve stimulation were significantly greater in arteries from cholesterol-fed as compared with those from control rabbits. Responses to adrenergic nerve stimulation of rings without endothelium were not different between the two groups. Methylene blue, a guanylate cyclase inhibitor, increased contractions of rings with endothelium and abolished the difference between the responses of arteries from cholesterol-fed and control rabbits. Methylene blue had no significant effect on arteries without endothelium. The overflow of endogenous norepinephrine (NE) caused by transmural electrical stimulation was not different between segments of arteries from cholesterol-fed and control rabbits. In control rabbits, exogenously applied NE contracted arteries with endothelium less than arteries without endothelium, whereas in cholesterol-fed rabbits the contractions caused by NE were not different between arteries with and without endothelium. Acetylcholine-induced relaxations were not different between rings with endothelium from cholesterol-fed and control rabbits. These results suggest that hypercholesterolemia selectively impairs the inhibitory influence of the endothelium on adrenergic contractions.