Urodilatin (ularitide, INN): a potent bronchodilator in asthmatic subjects

Atrial natriuretic peptide (CDD/ANP-99-126) has been identified as a bronchodilator in various species including humans. We investigated the effect of urodilatin (CDD/ANP-95-126) in 18 clinically stable asthmatics showing an increase of the FEV1 by > or = 15% after salbutamol inhalation. Prior to the study inhaled beta 2-agonists were withheld for 8 h. After baseline measurements of lung function parameters (FEV1, VC, PEF, MEF75, MEF50, MEF25), blood pressure, and heart rate in intravenous infusion of 20, 40 or 60 ng kg-1 min-1 urodilatin was administered for 40 min in the morning. All measurements were repeated every 10 min during the infusion, for 30 min thereafter, and after the inhalation of 1.25 mg salbutamol. Forty and 60 ng kg-1 min-1 urodilatin showed a significant effect on the central (FEV1, PEF, MEF75) and peripheral airways (MEF50, MEF25) after 10 min infusion (P < 0.05). A bronchodilation not significantly different from 1.25 mg salbutamol was induced by 40 ng kg-1 min-1 in the central airways only, while 60 ng kg-1 min-1 led to a similar effect at all levels of the bronchial tree. Lung function parameters returned to baseline within 30 min after cessation of the urodilatin infusion. Heart rate showed a tendency to increase after 40 min infusion (P < 0.05), but blood pressure did not change significantly. In conclusion, the maximal bronchodilating effect of intravenous urodilatin in clinically stable asthmatics was comparable to 1.25 mg salbutamol.