Bronchoconstrictor and antibronchoconstrictor properties of inhaled prostacyclin in asthma.
Prostacyclin (PGI2) is generated in appreciable amounts during allergic reactions in human lung tissue. To define its activity on human airways we have studied the effects of doubling concentrations of inhaled PGI2 and its hydrolysis product 6-oxoprostaglandin F1 alpha (6-oxo-PGF1 alpha) on specific airway conductance (sGaw), maximum expiratory flow at 30% vital capacity (Vmax30), forced expiratory volume in 1 s (FEV1), and static lung volumes in subjects with mild allergic asthma. In a second study the effect of inhaled PGI2 on bronchoconstriction provoked by increasing concentrations of inhaled prostaglandin (PG) D2 and methacholine was observed. Inhalation of PGI2 up to a concentration of 500 micrograms/ml had no significant effect on sGaw but produced a concentration-related decrease in FEV1 and Vmax30 in all subjects. In two of four subjects inhalation of PGI2 also increased residual volume and decreased vital capacity but had no effect on total lung capacity. PGI2, but not 6-oxo-PGF1 alpha, protected against bronchoconstriction provoked by either PGD2 or methacholine whether airway caliber was measured as sGaw, FEV1, or Vmax30. The apparent disparity between the bronchoconstrictor and antibronchoconstrictor effects of PGI2 might be explained by its potent vasodilator effect in causing airway narrowing through mucosal engorgement and reducing the spasmogenic effects of other inhaled mediators by increasing their clearance from the airways.
Hardy
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CC
Medicine 1 and Clinical Pharmacology, Southampton General Hospital, United Kingdom.
Bradding
P
P
Robinson
C
C
Holgate
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ST
D015121:6-Ketoprostaglandin F1 alpha / Q000494:pharmacology; D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D011464:Epoprostenol / Q000494:pharmacology*; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008448:Maximal Expiratory Flow Rate; D016210:Methacholine Chloride; D008688:Methacholine Compounds; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000494:pharmacology; D012119:Respiration / Q000187:drug effects; D014797:Vital Capacity / Q000187:drug effects
D008688:Methacholine Compounds; D011457:Prostaglandins D; D016210:Methacholine Chloride; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D015230:Prostaglandin D2