AIRWAY AND CARDIOVASCULAR-RESPONSES TO INHALED PROSTACYCLIN IN NORMAL AND ASTHMATIC SUBJECTS

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Abstract
Prostacyclin (PGI2) is one of several prostanoids released after antigen challenge of human lung fragments. To define its activity on human airways, the effect of inhaled PGI2 were studied 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 cAMP 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 mm Hg) and increase in heart rate (29 .+-. 3 beats .cntdot. min-1) with a small late fall in systolic blood pressure (8 .+-. 2 mm Hg). 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 2-fold increase in plasma levels of cAMP maximal at 5 min. Inhaled PGI2 at concentrations that had pronounced cardiovascular activity produced no consistent effect on airway caliber in normal or asthmatic subjects.