Abstract

The characteristics of uptake and efflux of ¹⁴C-labeled procaine and lidocaine have been examined in isolated aortic strips from rabbits. Significant differences were found in the tissue distribution of these local anesthetics. Lidocaine was accumulated by the smooth muscle to a greaten extent than procaine. 5,5-Dimethyl-2,4-oxazolidinedione-¹⁴C distni bution was used to estimate intracellular pH (pHi). The pHi was found to be 7.12 under control conditions (extracellulan pH = 7.2). The addition of procaine (1 mM) increased pHi to 7.23, whereas lidocaine (1 mM) was without effect on pHi. Procaine (1 mM) was found to be most potent against norepinephrine-induced tension and least potent against K⁺-induced tension. Effects of four local anesthetics (procaine, cocaine, tetnacaine and lidecaine) on ⁴⁵Ca spaces in Ca-free physiological salt solution correlated significantly with dissociation constants (pK_a) for the agents. On the basis of these findings, a dual site of action of local anesthetics on vascular smooth muscle is proposed. The cationic form of local anesthetics appears to act en the membrane to enhance caclium binding. The free base penetrates into cells and once inside may alter excitation-contraction coupling.