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⁺]₁ (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 μM 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. Conclusions: Primary alcohols produce reversible, complete relaxation of ASM, with potency increasing as chain length increases, by decreasing [Ca²⁺]_i and inhibiting increases in Ca²⁺ sensitivity produced by muscarinic receptor stimulation. These actions mimic those of volatile anesthetics on ASM, a circumstance suggesting that the primary alcohols may be useful tools for further exploring mechanisms of anesthetic effects on ASM.