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Decreased Arginine Bioavailability and Increased Serum Arginase Activity in Asthma

Department of Emergency Medicine and Pediatric Clinical Research Center, Children's Hospital and Research Center at Oakland, Oakland; Children's Hospital Oakland Research Institute, Oakland, CA; and Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA

Correspondence and requests for reprints should be addressed to Claudia R. Morris, M.D., Department of Emergency Medicine, Children's Hospital and Research Center at Oakland, 747 52nd Street, Oakland, CA 94609. E-mail: claudiamorris{at}comcast.net

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 µM, p < 0.0001), and serum arginase activity was elevated (1.6 ± 0.8 vs. 0.5 ± 0.3 µmol/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.

Key Words: asthmatic • L-arginine • amino acids • nitric oxide • nitric oxide synthase

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