Contraction of passively sensitized human bronchus induced by antigen challenge in vitro, was reduced by the prostaglandin F2α synthetase inhibitor, indomethacin. Prostaglandin F2α was released during challenge and this release was inhibited by indomethacin. There was a significant correlation between prostaglandin F2α release and antigen challenge‐induced contraction, suggesting that this substance may contribute to the bronchoconstrictor response of sensitized human bronchus to antigen.

1. Changes in specific airway conductance after the inhalation of aerosols of prostaglandins (PG) E1, E2, and F2alpha were investigated in healthy and asthmatic subjects. 2. Inhalation of 155 nmol (55 mug) of PGE1 or 156 nmol (55 mug) of PGF2 resulted in consistent minor bronchodilatation in healthy subjects, but in asthmatic patients airway conductance increased significantly, along with subjective improvement. Isoprenaline (988 nmol; 550 mug) inhalation resulted in a similar increase in conductance to that obtained after these two prostaglandins, whereas a control aerosol had no effect. In contrast to the isoprenaline aerosol, both PGE1 and PGF2 were highly irritant to inhale. It was concluded that this made them unsuitable for therapeutic use. 3. Prostaglandin F2alpha inhalation resulted in a dose-related bronchoconstriction in healthy and asthmatic subjects. Asthmatics were approximately 150 than were the healthy subjects but there was very wide and significant variantion in the sensitivity of the asthmatic subjects. In contrast the asthmatic subjects were only 8-5 times more sensitive to histamine than the healthy subjects with less variation in response of individual subjects. The reasons for the hyper-reactivity of asthmatic subjects to PGF2alpha is unknown and no correlation could be drawn between increased sensitivity and age, type of asthma, or treatment. 4. The effects of disodium cromoglycate, flufenamic acid, atropine methonitrate, PGF2 and isoprenaline on PGF2alpha-induced bronchoconstriction were investigated in healthy subjects. Prostaglandin E2 reversed PGF2alpha-induced bronchoconstriction, as did isoprenaline, but prior treatment with the other drugs had no effect in preventing bronchoconstriction.

We have investigated the effects of the calcium antagonist nifedipine on antigen-induced bronchoconstriction in vivo and in vitro. Eight grass-pollen-sensitive asthmatics were given either nifedipine (20 mg sublingually) or placebo 30 min before antigen challenge. The fall in forced expiratory volume in one second after pretreatment with placebo was 42.8 +/- 10.1%. After nifedipine this fall was significantly reduced to 26.5 +/- 11.7% (p less than 0.005). Two in vitro models of allergic asthma have been studied: actively sensitized guinea pig tracheal strips (GPT) and passively sensitized human bronchial muscle (HBM). Contraction of GPT by acetylcholine, histamine, and antigen challenge was unaffected by nifedipine 10(-4)M. Contraction of HBM by acetylcholine, histamine and grass pollen antigen challenge was significantly reduced by nifedipine 10(-4)M and 10(-6)M. The magnitude of the reduction in contraction to antigen challenge was comparable to the inhibition of acetylcholine and histamine responses. It would appear most likely that nifedipine exerts its effect mainly on bronchial muscle contractility rather than by stabilizing mast cells.

The effect of pretreatment with prostaglandin F2 alpha (PGF2 alpha) on the bronchial sensitivity to histamine and methacholine has been studied in three groups of six normal subjects, and compared with the effect of citric acid aerosol as a non-specific stimulant of bronchial irritant receptors. Aerosols were generated by Wright's nebulizer and dose-response curves to histamine and methacholine constructed following preadministration of saline, prostaglandin F2 alpha or citric acid. Following prostaglandin F2 alpha pretreatment, the PC20 histamine fell from 12.9 mg/ml to 3.4 mg/ml (P less than 0.01), but the PC20 methacholine was unchanged. Citric acid was without effect. The results indicate that prostaglandin F2 alpha can increase bronchial sensitivity to inhaled histamine, possibly via a direct effect on the airway smooth muscle.

No abstract