HIGH-DOSE INHALED ATRIAL-NATRIURETIC-PEPTIDE IS A BRONCHODILATOR IN ASTHMATIC SUBJECTS

Atrial natriuretic peptide (ANP) has been shown to be an effective bronchodilator when given intravenously, but its efficacy by inhalation has not been assessed. In the first part of the current study, six asthmatic subjects, mean (SEM) forced expiratory volume in one second (FEV(1)) 2.09 (0.30) l, received 0.1 and 1 mg atrial natriuretic peptide by inhalation, and in the second study five subjects, FEV(1) 1.92 (0.40) l, received 5 mg ANP by inhalation. ANP was given in a placebo-controlled, double blind, randomized manner, with measurement of FEV(1) over the following 60 min. Nebulized salbutamol was given at 60 min as a measure of the maximal bronchodilator response attainable by conventional therapy. No significant bronchodilator effect was seen following the 0.1 or 1 mg inhalation, although the latter produced a minimal transient elevation in peripheral atrial natriuretic peptide plasma levels. A bronchodilator effect was seen with the 5 mg dose, which produced Delta FEV(1) 0.42 (0.09) l compared to 0.93 (0.13) l subsequently produced by salbutamol. This effect peaked at 5 min and was no different from placebo from 10 min onwards. We conclude that atrial natriuretic peptide may produce significant bronchodilation when given by inhalation in high doses, and speculate that substances which generate cyclic guanosine monophosphate (cGMP) in airway smooth muscle warrant further investigation as potential bronchodilatory agents.