Inhaled L-arginine improves exhaled nitric oxide and pulmonary function in patients with cystic fibrosis.
BACKGROUND
Nitric oxide formation is deficient in airways of patients with cystic fibrosis (CF). Since nitric oxide has bronchodilatory effects, nitric oxide deficiency may contribute to airway obstruction in CF.


OBJECTIVE
We reasoned that inhalation of l-arginine, the precursor of enzymatic nitric oxide formation, could improve airway nitric oxide formation and pulmonary function in patients with CF.


METHODS
Exhaled nitric oxide, pulmonary function, and peripheral oxygen saturation were measured before and after a single inhalation of nebulized l-arginine solution in patients with CF and in healthy subjects. A saline solution of similar osmolarity (1.7%) was used as control.


RESULTS
Nebulized l-arginine not only significantly increased exhaled nitric oxide concentrations but also resulted in a sustained improvement of FEV(1) in patients with CF. Oxygen saturation also increased significantly after the inhalation of l-arginine. Nebulized saline resulted in a small but significant increase in exhaled nitric oxide but a decrease in FEV(1) in patients with CF. In control subjects inhalation of l-arginine increased exhaled nitric oxide concentrations, but FEV(1) decreased. No effect of saline on exhaled nitric oxide, pulmonary function, or oxygen saturation was observed in healthy subjects.


CONCLUSIONS
These data suggest that a single inhalation of l-arginine acutely and transiently improves pulmonary function in CF through the formation of nitric oxide. Augmentation of airway nitric oxide formation by inhalation of l-arginine is a promising therapeutic approach in patients with CF.
Grasemann
Hartmut
H
The Hospital for Sick Children, Division of Respiratory Medicine, 555 University Ave., Toronto, ON, M5G 1X8 Canada. hartmut.grasemann@sickkids.ca
Kurtz
Fionn
F
Ratjen
Felix
F
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000008:administration & dosage*; D001944:Breath Tests; D002956:Citrulline / Q000097:blood; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis*; D009952:Ornithine / Q000097:blood; D010865:Pilot Projects; D019141:Respiratory System Agents / Q000008:administration & dosage*
D019141:Respiratory System Agents; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine; D009952:Ornithine