Hartmut Grasemann1, Fionn Kurtz, Felix Ratjen. 1. The Hospital for Sick Children, Division of Respiratory Medicine, 555 University Ave., Toronto, ON, M5G 1X8 Canada. hartmut.grasemann@sickkids.ca
Abstract
RATIONALE: 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. OBJECTIVES: 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. MEASUREMENTS: 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.
RATIONALE: 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. OBJECTIVES: 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. MEASUREMENTS: 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.
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