Decreased systemic bioavailability of L-arginine in patients with cystic fibrosis

Background: L-arginine is the common substrate for nitric oxide synthases and arginases. Increased arginase levels in the blood of patients with cystic fibrosis may result in L-arginine deficiency and thereby contribute to low airway nitric oxide formation and impaired pulmonary function. Methods: Plasma amino acid and arginase levels were studied in ten patients with cystic fibrosis before and after 14 days of antibiotic treatment for pulmonary exacerbation. Patients were compared to ten healthy non-smoking controls. Results: Systemic arginase levels measured by ELISA were significantly increased in cystic fibrosis with exacerbation compared to controls (17.3 +/- 12.0 vs. 4.3 +/- 3.4 ng/ml, p<0.02). Arginase levels normalized with antibiotic treatment. Plasma L-arginine was significantly reduced before (p<0.05) but not after treatment. In contrast, L-ornithine, proline, and glutamic acid, all downstream products of arginase activity, were normal before, but significantly increased after antibiotic therapy. Bioavailability of L-arginine was significantly reduced in cystic fibrosis before and after exacerbation (p<0.05, respectively). Conclusion: These observations provide further evidence for a disturbed balance between the L-arginine metabolic pathways in cystic fibrosis.