Airway and cardiovascular responses to inhaled prostacyclin in normal and asthmatic subjects.
Prostacyclin (PGI2) is one of several prostanoids released after antigen challenge of human lung fragments. To define its activity on human airways, we studied the effect of inhaled PGI2 in 10 normal and 8 asthmatic subjects. In random order, PGI2, 1 mg/ml, its hydrolysis product, 6-oxo-PGF1 alpha, 1 mg/ml, and glycine vehicle were given on separate occasions by nebulizer. Measurements of specific airway conductance (SGaw), blood pressure (BP), heart rate (HR), plasma 6-oxo-PGF1 alpha, and cyclic AMP levels were made at frequent intervals for as long as 45 min after nebulization. Prostacyclin and 6-oxo-PGF1 alpha caused cough and retrosternal discomfort. None of the drugs had any significant effect on SGaw in either the normal or asthmatic subjects, though 2 asthmatics showed consistent bronchodilatation with prostacyclin. Prostacyclin caused a marked fall in diastolic blood pressure (mean 20 +/- 3 mmHg) and increase in heart rate (29 +/- 3 beats X min-1) with a small late fall in systolic blood pressure (8 +/- 2 mmHg). This was associated with a 12- to 15-fold increase in plasma 6-oxo-PGF1 alpha levels maximal at 1 min, and in normal subjects only, a later twofold increase in plasma levels of cyclic AMP maximal at 5 min. Thus, inhaled PGI2 at concentrations that had pronounced cardiovascular activity produced no consistent effect on airway caliber in normal or asthmatic subjects.
Hardy
C
C
Robinson
C
C
Lewis
R A
RA
Tattersfield
A E
AE
Holgate
S T
ST
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000328:Adult; D000336:Aerosols; D001249:Asthma / Q000097:blood / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D000242:Cyclic AMP / Q000097:blood; D011464:Epoprostenol / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D012123:Pulmonary Ventilation / Q000187:drug effects*; D012016:Reference Values; D014680:Veins
D000336:Aerosols; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D000242:Cyclic AMP