Effects of bupivacaine and its isomers on guinea pig tracheal smooth muscle.

The effects of racemic bupivacaine and its (-)-(S)- and (+)-(R)-isomers on guinea pig tracheal smooth muscle tension were studied in vitro. Racemic bupivacaine had a dual action with contraction at low concentrations (6.9-55 x 10(-6) M) and relaxation at high concentrations (1.1-18 x 10(-4) M), (-)-(S)-Bupivacaine had dual action comparable to that of racemic bupivacaine, while (+)-(R)-bupivacaine had only weak contractile effects with more marked relaxant effects. The contractile effects of bupivacaine were abolished in Ca(2+)-free medium and by verapamil, while the relaxant effects were not influenced by verapamil or Ca(2+)-free medium. The (-)-(S)-isomer is responsible for the contractile effects of racemic bupivacaine, whereas both (-)-(S)- and (+)-(R)-isomers contribute to its relaxant effects. In preparations denuded of epithelium, the (maximal) responses were attenuated to 86% of maximum contraction and 48% of maximum relaxation, suggesting that the epithelium plays a larger role in relaxant than in contractile responses to bupivacaine. It is concluded that bupivacaine has a dual action on guinea pig tracheal smooth muscle with epithelium-independent. Ca(2+)-dependent contraction at low concentrations and epithelium-dependent, Ca(2+)-independent relaxation at higher concentrations.