Inhibitory effects of bupivacaine and lidocaine on adrenergic neuroeffector junctions in rat tail artery

Various local anesthetic agents have been shown to cause relaxation of isolated vascular segments contracted by catecholamines and other constrictor drugs. This report describes the actions of the amide-linked local anesthetic, bupivacaine, on adrenergic responsiveness of isolated arterial smooth muscle, and compares bupivacaine effects with those of lidocaine.

Helical strips of rat tail artery mounted in a muscle bath for measurement of isometric force generation were contracted in response to adrenergic nerve stimulation, increased potassium concentration, tyramine, or exogenous norepinephrine.

Treatment with bupivacaine or lidocaine caused depression of contraction to all four stimuli. Contraction to adrenergic nerve stimulation was more sensitive to the inhibitory effects of local anesthetics than was contraction to elevated potassium, tyramine, or exogenous norepinephrine. Furthermore, bupivacaine was more effective in reducing contraction to adrenergic nerve stimulation than was lidocaine (EC50: bupivacaine = 4 x 10(-6) M; lidocaine = 61 x 10(-6) M). In arteries incubated in solutions containing [3H]-norepinephrine and mounted for superfusion and isometric force recording, both bupivacaine and lidocaine (10(-5) M) depressed the contractions and diminished the release of radioactivity evoked by nerve stimulation. At the concentration tested, bupivacaine was more effective than lidocaine in reducing both contraction and the efflux of radioactivity as indicated by the magnitude of depression compared with control activities.

These findings suggest that lidocaine and bupivacaine depress adrenergic neurotransmission and inhibit smooth muscle contraction. Bupivacaine is a more potent inhibitor of adrenergic neurotransmission in the blood vessel wall than is lidocaine.