Inhibition of adenosine 5'-monophosphate- and methacholine-induced bronchoconstriction in asthma by inhaled frusemide

Recent studies have shown that inhaled frusemide exerts a protective effect against various bronchoconstrictor stimuli in asthma including exercise, fog and allergen. Since mast cell activation seems to be a component of bronchoconstriction by these stimuli it is possible that inhibition of mediator release accounts for some or all of the inhibitory effects of frusemide in asthma. Since inhaled adenosine 5'-monophosphate (AMP) is another stimulus that produces bronchoconstriction by augmenting mast cell mediator release, we have investigated the ability of this drug to antagonise the airway effects of inhaled AMP and methacholine in a randomized, placebo-controlled, double-blind study of 12 asthmatic subjects. Inhaled frusemide (approximately 28 mg) administered 5 min prior to challenge increased the provocation concentration of inhaled AMP and methacholine required to reduce forced expiratory volume in one second (FEV) by 20% from baseline from 30 to 96 mg.ml-1 (p less than 0.01) and from 1.1 to 1.8 mg.ml-1 (p less than 0.01), respectively. The protection that frusemide afforded against AMP was significantly greater than that against methacholine (p less than 0.05). These data suggest that inhaled frusemide may serve as a functional antagonist against a smooth muscle spasmogen, such as methacholine, possibly by augmenting prostanoid generation. Its more potent activity against AMP and other bronchoconstrictor stimuli, that are considered to involve mast cell mediators, suggests an additional action on mast cell functions possibly at the level of the Ca++/Mg(++)-ATPase.

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