Recent studies suggest that a
nitric oxide (NO) deficiency and elevated
arginase activity may play a role in the pathogenesis of
asthma. Although much attention has been directed toward measurements of exhaled NO in
asthma, no studies to date have evaluated levels of plasma
arginase or
arginine, the substrate for NO production, in patients with
asthma. This study, therefore, measured
amino acid levels,
arginase activity, and
nitric oxide metabolites in the blood of patients with
asthma, as well as NO in exhaled breath. Although levels of virtually all
amino acids were reduced, patients with
asthma exhibited a striking reduction in plasma
arginine levels compared with normal control subjects without
asthma (45 +/- 22 vs. 94 +/- 29 microM, p < 0.0001), and serum
arginase activity was elevated (1.6 +/- 0.8 vs. 0.5 +/- 0.3 micromol/ml/hour,
asthma vs. control, p < 0.0001). High
arginase activity in patients with
asthma may contribute to low circulating
arginine levels, thereby limiting
arginine bioavailability and creating a NO deficiency that induces hyperreactive airways. Addressing the alterations in
arginine metabolism may result in new strategies for treatment of
asthma.