Bronchodilating effects of natriuretic and vasorelaxant peptides compared to salbutamol in asthmatics.
In animal studies, the bronchial effects of urodilatin (URO, CDD/ANP-95-126, INN: ularitide) were superior to those of cardiodilatin/atrial natriuretic peptide (CDD, CDD/ANP-99-126). We compared the bronchodilating properties of intravenous URO and CDD in 36 clinically stable asthmatics showing a beta 2-agonist-induced increase of the FEV1 by > or = 15%. Any aerosol medication was discontinued for at least 8 h prior to the study. After baseline measurements of lung function parameters (FEV1, VC, PEF, MEF75, MEF50, MEF25) an intravenous infusion of 5.7, 11.4 or 17.1 pmol/kg/min URO or CDD 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 (SALB). Both peptides had significant effects. While 11.4 pmol/kg/min URO dilated the central airways (FEV1, PEF, MEF75) slightly more potently than the peripheral bronchioles (MEF50, MEF25), 17.1 pmol/kg/min URO was as effective as SALB at all levels of the tracheobronchial tree. CDD reached only 50% of the SALB effect without a predominant localization of its action. The cardiovascular parameters revealed a significantly stronger vasorelaxant activity of CDD. In conclusion, the dose-dependent bronchodilating properties of intravenous URO were significantly superior to those of CDD.
Flüge
T
T
Department of Respiratory Medicine, Hannover Medical School, Germany.
Fabel
H
H
Wagner
T O
TO
Schneider
B
B
Forssmann
W G
WG
D000328:Adult; D000420:Albuterol / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D012123:Pulmonary Ventilation / Q000187:drug effects*; D012129:Respiratory Function Tests; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
D001993:Bronchodilator Agents; D009124:Muscle Proteins; D010446:Peptide Fragments; D014665:Vasodilator Agents; C056452:Ularitide; D009320:Atrial Natriuretic Factor; C040651:cardiodilatin; D000420:Albuterol