The effect of local anesthetic, lidocaine, on guinea pig trachealis muscle in vitro.

The effect of lidocaine was studied in guinea pig trachealis muscle by dose-response reversal and protection of agonist-induced contractures in a superfusion system. Lidocaine reversed histamine, acetylcholine, and depolarizing hypertonic potassium contractures with the median effective doses of 2.8, 6.0, and 3.2 mg. Lidocaine presuperfusion shifted in a nonparallel fashion (P less than 0.05) the dose-response of histamine, acetylcholine, depolarizing potassium, and supramaximal electrical stimulation by contact electrodes. Pretreatment with 7 x 10(-6) M atropine did not modify lidocaine's inhibition of the hypertonic potassium contractions. These findings and the decrease in maximal response indicated noncompetitive antagonism. In contrast to isoproterenol, the action of lidocaine was not influenced by beta-blockade induced by superfusate propranolol, 1.0 mug per ml (P = 0.2). Lidocaine's effect on trachealis smooth muscle was facilitated by a decrease in hydrogen ion activity from pH 6.71 to 7.90, consistent with enhanced penetration of the free base. Low bolus dose lidocaine-induced contractures were noted in many studies. The potency of isoproterenol in comparison to lidocaine, as indexed by median effective doses, was 10(5) greater for reversal of histamine contractures and 10(4) greater for acetylcholine. The data were consistent with a nonspecific, reversible antagonism on the smooth muscle cell and may involve an effect on calcium activity.