Increased Uptake of Methylated Low-Density Lipoprotein Induced by Noradrenaline in Carotid Arteries of Anaesthetized Rabbits

Atherosclerosis is accelerated in hyperlipidaemias but, apart from the concentration of low-density lipoprotein (LDL) in the blood, very little is known about other influences on the disease process. We now provide evidence that in anaesthetized rabbits the atherogenic uptake of LDL by arterial walls is accelerated by noradrenaline at its physiological concen­trations in rabbit and human blood. The principle of the experiments was to compare the uptake of intra­venously injected, radioactively labelled LDL, methylated to prevent removal by high-affinity receptors, in the two carotid arteries of anaes­thetized rabbits after infusing low concentrations of noradrenaline into one carotid and saline as control into the other, the volume rates of infusion being about 1% of the carotid blood flows. Human LDL, which behaves sufficiently like rabbit LDL for these purposes, was prepared, methylated and radio-iodinated by standard methods. At the end of the infusions, the arteries were excised and their radio activities determined. Noradrenaline infused for 2 h to produce local blood concentrations of nominally 1, 10, 50 and 100 nM significantly increased the LDL radio­ activities of the walls of the noradrenaline-infused carotids. Concen­trations of nominally 100 nM also increased the LDL radioactivities of the walls of the saline-infused carotids; this was associated with significant increases in their blood noradrenaline concentrations. These results may contribute towards an explanation for the acceler­ated atherosclerosis and the increased incidence of its clinical manifes­tations in conditions associated with elevated blood noradrenaline concentrations, including the episodic increases associated with stress and cigarette smoking as well as the more persistent increases caused by phaeochromocytoma.