Membrane-active agents. Effect of various anesthetics and chlorpromazine on arterial lipid metabolism

The local anesthetic lidocaine was studied for its effects on lipid metabolism in aortas from normal rats, rabbits, and cholesterol-fed (atherosclerotic) rabbits in vitro. Incubation of aortas in the presence of 3--5 mM lidocaine resulted in a statistically significant reduction in the incorporation of [14C]oleate into cholesteryl esters and phosphatidylcholine. Additionally, significant increases in [14C]oleate incorporation into the diglyceride fraction of atheromatous rabbit aortas was observed with a trend to greater incorporation into the diglyceride fraction of normal rat and rabbit arteries as well. The most significant overall effect of lidocaine was its inhibition (50--90%) of the arterial sterol esterification. Assays of acylCoA : cholesterol acyltransferase (ACAT, EC 2.3.1.26) in isolated arterial microsomes revealed that, in addition to local anesthetics (e.g., lidocaine), other membrane-active agents such as chlorpromazine and methoxyflurane inhibit ACAT; this suggests ACAT may be regulated by alterations in the biophysical properties of its membrane milieu.