Effects of Primary Alcohols on Airway Smooth Muscle

Background: The investigation examined whether primary alcohols could be used as tools to explore the mechanism of anesthetic actions in airway smooth muscle (ASM). The hypothesis was that, like volatile anesthetics, the primary alcohols relax intact ASM by decreasing intracellular Ca2+ concentration (Ca2+]i) and by inhibiting agonist-induced increases in the force developed for a given Ca2+]i (Ca2+ sensitivity).

Method: The effects of butanol, hexanol, and octanol on isometric force in canine tracheal smooth muscle were examined. The effects of hexanol on Ca2+]i (measured with fura-2) and the relationship between force and Ca2+]i were studied during membrane depolarization provided by KCl and during muscarinic stimulation provided by acetylcholine.

Results: The primary alcohols relaxed ASM contracted by KCl or acetylcholine in a concentration-dependent manner, with potency increasing as chain length increased. The alcohols could completely relax the strips, even during maximal stimulation with 10 mu]m acetylcholine (median effective concentrations of 28 +/- 12, 1.3 +/- 0.4, and 0.14 +/- 0.05 mm mean +/- SD] for butanol, hexanol, and octanol, respectively). Hexanol decreased both Ca2+]i and force in a concentration-dependent manner. Hexanol decreased Ca2+ sensitivity during muscarinic stimulation but had no effect on the force-Ca2+]i relationship in its absence.