Relaxation of tracheal smooth muscle independent on functional epithelium cells induced by lidocaine, bupivacaine and isomers in rats

Lidocaine is a local anesthetic which has been used to protect spasm reaction during tracheal intubation and bronchoscopy. We compared the potency of lidocaine, bupivacaine (RS(±)-bupivacaine) and isomers (S(−)-bupivacaine and R(+)-bupivacaine) to promote relaxation of tracheal smooth muscle. Relaxation of airways smooth muscle can be dependent on the release of relaxing factors by epithelium such as prostanoids and nitric oxide (NO). Possible mechanisms involved in the tracheal smooth muscle relaxation induced by these local anesthetics were evaluated in preparation in which the epithelium layer was intact or denuded. Bupivacaine and its isomers were approximately six to eleven-fold more potent than lidocaine to promote relaxation on acetylcholine-induced contraction in tracheal rings. The concentration of lidocaine, RS(±)-bupivacaine, S(−)-bupivacaine and R(+)-bupivacaine necessary to produce a 50% reduction of maximal contraction to acetylcholine (IC50) in tracheal rings with intact epithelium was 1.25 ± 0.01, 0.11 ± 0.01, 0.15 ±0.01, 0.19 ± 0.01 mM, respectively. Removal of epithelium or exposure to NG-nitro-L-arginine methyl ester, indomethacin did not alter the IC50. However, calcium influx of depolarized tracheal smooth muscle was inhibited by lidocaine, bupivacaine and isomers. S(−)-bupivacaine reduced by 78.8 ± 7.4% the calcium influx followed by RS(±)-bupivacaine (41.8 ± 6.7%) and R(+)-bupivacaine (25.6 ± 9.5%). In conclusion, local anesthetic action was stereoselective and partially dependent on blockade of Ca2+ influx to muscular cells. The isomer S(−)-bupivacaine is more potent and less toxic which could represent a valuable clinical advantage to use as broncholitic agent.