Journal of Applied Physiology, Vol 54, Issue 1 105-112, Copyright © 1983 by American Physiological Society
Novel effects of PGF2 alpha on airway function in asthmatic subjects
J. E. Fish, H. H. Newball, P. S. Norman and V. I. Peterman
The effects of inhaled prostaglandin F2 alpha (PGF2 alpha) have been
examined in eight subjects with asthma. Incremental PGF2 alpha aerosol
concentrations, ranging from 1 to 5,000 micrograms/ml, were administered at
15-min intervals. Plethysmographic specific airway conductance (sGaw),
forced expiratory volume at 1 s (FEV1), and maximum expiratory flow at 50%
vital capacity breathing air (Vmax50% air) and 80% He-20% O2 (Vmax50%
He-O2) were measured after each dose and compared with saline control
values. We observed unexpected triphasic dose-response characteristics,
i.e., an initial decline in physiological variables at low concentrations
(1-100 micrograms/ml), followed by improvement at intermediate
concentrations (100-1,000 micrograms/ml) and a subsequent steep decline at
high concentrations (1,000-5,000 micrograms/ml). Improvement in FEV1 and
Vmax50% air between 100 and 1,000 micrograms/ml was associated with sGaw
increases above control levels in six subjects and a significant fall in
density-dependent index (Vmax50% He-O2/Vmax50% air) when compared with
values before challenge and at low concentrations. Inhaled atropine (5 mg)
improved prechallenge lung function but had no effect on PGF2 alpha
dose-response characteristics. Intermediate PGF2 alpha concentrations given
as a single dose consistently induced greater FEV1 reductions than the same
concentration during graded dose challenges. Our findings are consistent
with the demonstration of in vivo airway tachyphylaxis and indicate that
airway effects of PGF2 alpha are far more complex than previously reported.
Moreover, these novel effects suggest that, in addition to its well-known
bronchoconstrictor effects, PGF2 alpha directly or indirectly causes airway
relaxation, predominantly in large airways.
