BACKGROUND: Etomidate is an intravenous anesthetic which has properties of hemodynamic stability, minimal respiratory depression, and cerebral protection. Also, it is a useful induction agent for patients compromised by asthma and other reactive airway diseases. The aim of this study was to investigate the effect and action mechanism of etomidate on isolated tracheal smooth muscle in rats. METHODS: The rat's trachea was dissected free, cut into rings (2 mm) and mounted for isometric tension in Tris Tyrode solution. Cumulative dose-response curves for etomidate (3 X 10(-7) 3 X 10 (-4) M) were obtained from the tension measurements of acetylcholine (10 (-5)M)-contracted rings. The effects of propranolol, L-NAME and indomethacin on the etomidate induced tracheal response were investigated. Also, the effect of etomidate on the extracellular Ca2+ influx and Ca2+ release from internal stores was investigated. RESULTS: Etomidate produced relaxation of acetylcholine-precontracted trachea in a dose-dependent fashion. Pretreatment with propranolol, L-NAME had no effects on concentration-response curves to acetylcholine. Pretreatment with indomethacin had an effect on the concentration-response curve to acetylcholine. Pretreatment with etomidate inhibited acetylcholine-induced contractions in the absence of extracelluar Ca2+ and the presence of extracellular Ca2+ . CONCLUSIONS: The tracheal smooth muscle relaxation by etomidate is not related with beta-adrenergic activation and NO synthesis but related with prostaglandin production. The relaxation effect of etomidate is induced by a decrease in concentration of intracellular Ca2+ through the blockade of extracellular Ca2+ influx and the simultaneous release of Ca2+ from internal stores.