Bronchodilation using combined urodilatin - albuterol administration in asthma: a randomized, double-blind, placebo-controlled trial.
Urodilatin, the renal form of natriuretic peptide type A, induces bronchodilation, increasing intracellular cyclic guanosine monophosphate (cGMP), whereas the bronchorelaxant effect by b2-agonists is triggered by cyclic adenosine monophosphate (cAMP). The objective of this investigation is to demonstrate the efficacy of urodilatin in inducing bronchodilation, and to show this activity alone or in combination with albuterol. Therefore, a randomized, double-blind, placebo-controlled, dose-finding study with cross-over design was carried out including 12 stable, mild to severe (step 2 to 4, definition by NIH/NHLBI guideline 1997) asthmatics. 96 treatments were thus performed. The intervention was comprised of an intravenous infusion of urodilatin (0, 10, 30, or 60 ng/kg/min) combined with inhaled albuterol (0 or 200 microg). As primary objective, the increase in forced expiratory volume in one second (FEV subset1) was measured. - The trial shows that urodilatin at all applied doses or 200 microg albuterol significantly increases FEV subset1 (p < 0.05). Combination of urodilatin and albuterol treament significantly improves FEV subset1 (p < 0.05) compared to either monotherapy and results in maximum bronchodilation. - From the results, the following conclusions can be drawn. In stable asthmatics, the combined activation of cGMP- and cAMP-mediated pathways results in a significantly improved, maximal bronchodilation in comparison to either type of monotherapy. This shows that urodilatin combined with albuterol improves lung function and ameliorates the therapy in asthmatics.
Flüge
T
T
Lower Saxony Institute for Peptide Research, Feodor-Lynen-Strasse 31, D-30625 Hannover, Germany. wgforssmann@gmx.de.
Forssmann
W G
WG
Kunkel
G
G
Schneider
B
B
Mentz
P
P
Forssmann
K
K
Barnes
P J
PJ
Meyer
M
M
D000328:Adult; D000420:Albuterol / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000188:drug therapy*; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage* / Q000009:adverse effects; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D000242:Cyclic AMP / Q000502:physiology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects
D001993:Bronchodilator Agents; D010446:Peptide Fragments; C056452:Ularitide; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D000420:Albuterol