THE EFFECT OF LOCAL-ANESTHETICS ON ARTERIAL LIPID-METABOLISM - INHIBITION OF STEROL ESTERIFICATION INVITRO

The local anesthetics lidocaine, tetracaine, benzocaine and dibucaine inhibit sterol esterification by acylCo[coenzyme]A:cholesterol acyltransferase (EC 2.3.1.26) in the microsomal fraction isolated from rabbit aortas. In arterial microsomes, the incorporation of [14C]oleoylCoA into [14C]steryl esters was inhibited in a dose-dependent way by the anesthetics over the concentration range 0.25-5.0 mM. The potency of inhibition was dibucaine > benzocaine > tetracaine > lidocaine > procaine with inhibition of .apprx. 85% occurring with 0.25 mM dibucaine. Sterol esterification to [14C]oleic acid was inhibited by the anesthetics in intact aortic tissue from the rabbit, dog and rat. A detailed study of the effects of 5 mM lidocaine on lipid biosynthesis in the rabbit aorta in vitro revealed that lidocaine inhibited sterol esterification to [14C]oleate and stimulated [14C]oleate incorporation into glycerides. [Arterial lipid relation to atherogenesis is discussed.].