Relaxant effects of lithium on guinea-pig tracheal smooth muscle in vitro

The effect of lithium was studied on resting tension of guinea-pig spiral tracheal strips and their responses to carbachol and histamine in vitro. Lithium reversibly relaxed tracheal smooth muscle in a dose-dependent manner. In addition, lithium increased the ED50 for carbachol 10 fold and that for histamine by over 100 fold; maximum responses for each agonist were also reduced. Lithium-induced relaxation of tracheal smooth muscle was unaffected by changes in extracellular calcium concentration over the range 0-11 mM, verapamil, ouabain, procaine, propranolol or reduction in extracellular sodium concentration. The ability of lithium to reduce carbachol- and histamine-induced contraction of tracheal smooth muscle was also not altered by propranolol, procaine, ouabain, verapamil or lowered extracellular sodium. We conclude that lithium acts directly on tracheal smooth muscle to relax it by an as yet unknown mechanism. This may or may not be related to the ability of this agent to alter agonist-induced contraction of tracheal smooth muscle.