INHIBITORY EFFECTS OF BUPIVACAINE AND LIDOCAINE ON ADRENERGIC NEUROEFFECTOR JUNCTIONS IN RAT TAIL ARTERY

Background. Various local anesthetic agents have been shown to cause r elaxation of isolated vascular segments contracted by catecholamines a nd other constrictor drugs. This report describes the actions of the a mide-linked local anesthetic, bupivacaine, on adrenergic responsivenes s of isolated arterial smooth muscle, and compares bupivacaine effects with those of lidocaine. Methods: Helical strips of rat tail artery m ounted 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. Resul ts. Treatment with bupivacaine or lidocaine caused depression of contr action to all four stimuli. Contraction to adrenergic nerve stimulatio n was more sensitive to the inhibitory effects of local anesthetics th an was contraction to elevated potassium, tyramine, or exogenous norep inephrine. Furthermore, bupivacaine was more effective in reducing con traction to adrenergic nerve stimulation than was lidocaine (EC50: bup ivacaine = 4 x 10(-6) m; lidocaine = 61 X 10(-6) M). In arteries incub ated in solutions containing [H-3]-norepinephrine and mounted for supe rfusion and isometric force recording, both bupivacaine and lidocaine (10(-5) m) depressed the contractions and diminished the release of ra dioactivity evoked by nerve stimulation. At the concentration tested, bupivacaine was more effective than lidocaine in reducing both contrac tion and the efflux of radioactivity as indicated by the magnitude of depression compared with control activities. Conclusions. These findin gs suggest that lidocaine and bupivacaine depress adrenergic neurotran smission and inhibit smooth muscle contraction. Bupivacaine is a more potent inhibitor of adrenergic neurotransmission in the blood vessel w all than is lidocaine.