TY - JOUR
T1 - Novel effects of PGF(2α) on airway function in asthmatic subjects
AU - Fish, J. E.
AU - Newball, H. H.
AU - Norman, P. S.
AU - Peterman, V. I.
PY - 1983
Y1 - 1983
N2 - The effects of inhaled prostaglandin F(2α) (PGF(2α)) have been examined in eight subjects with asthma. Incremental PGF(2α) aerosol concentrations, ranging from 1 to 5,000 μg/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 (V̇max50% air) and 80% He-20% O2 (V̇max50% 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 μg/ml), followed by improvement at intermediate concentrations (100-1,000 μg/ml) and a subsequent steep decline at high concentrations (1,000-5,000 μg/ml). Improvement in FEV1 and V̇max50% air between 100 and 1,000 μg/ml was associated with sGaw increases above control levels in six subjects and a significant fall in density-dependent index (V̇max50% He-O2/V̇max50% air) when compared with values before challenge and at low concentrations. Inhaled atropine (5 mg) improved pre-challenge lung function but had no effect on PGF(2α) dose-response characteristics. Intermediate PGF(2α) 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 PGF(2α) are far more complex than previously reported. Moreover, these novel effects suggest that, in addition to its well-known bronchoconstrictor effects, PGF(2α) directly or indirectly causes airway relaxation, predominantly in large airways.
AB - The effects of inhaled prostaglandin F(2α) (PGF(2α)) have been examined in eight subjects with asthma. Incremental PGF(2α) aerosol concentrations, ranging from 1 to 5,000 μg/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 (V̇max50% air) and 80% He-20% O2 (V̇max50% 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 μg/ml), followed by improvement at intermediate concentrations (100-1,000 μg/ml) and a subsequent steep decline at high concentrations (1,000-5,000 μg/ml). Improvement in FEV1 and V̇max50% air between 100 and 1,000 μg/ml was associated with sGaw increases above control levels in six subjects and a significant fall in density-dependent index (V̇max50% He-O2/V̇max50% air) when compared with values before challenge and at low concentrations. Inhaled atropine (5 mg) improved pre-challenge lung function but had no effect on PGF(2α) dose-response characteristics. Intermediate PGF(2α) 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 PGF(2α) are far more complex than previously reported. Moreover, these novel effects suggest that, in addition to its well-known bronchoconstrictor effects, PGF(2α) directly or indirectly causes airway relaxation, predominantly in large airways.
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M3 - Article
C2 - 6826394
AN - SCOPUS:0020625549
SN - 0161-7567
VL - 54
SP - 105
EP - 112
JO - Journal of Applied Physiology Respiratory Environmental and Exercise Physiology
JF - Journal of Applied Physiology Respiratory Environmental and Exercise Physiology
IS - 1
ER -