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Published ahead of print on April 7, 2004, doi:10.1164/rccm.200309-1304OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 2, July 2004, 148-153

A more recent version of this article appeared on July 15, 2004
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Submitted on September 29, 2003
Accepted on April 3, 2004

Decreased Arginine Bioavailability and Increased Serum Arginase Activity in Asthma

Claudia R Morris1*, Mirjana Poljakovic2, Lisa Lavrisha3, Lorenzo Machado4, Frans A Kuypers4, and Sidney M Morris, Jr.2

1 Department of Emergency Medicine, Children's Hospital and Research Center at Oakland, Oakland, CA, USA, 2 Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA, 3 Pediatric Clinical Research Center, Chidren's Hospital and Research Center at Oakland, Oakland, CA, USA, 4 Children's Hospital Oakland Research Institute, Oakland, CA, USA

* To whom correspondence should be addressed. E-mail: claudiamorris{at}comcast.net.

Recent studies suggest that a nitric oxide deficiency and elevated arginase activity may play a role in the pathogenesis of asthma. Although much attention has been directed towards measurements of exhaled nitric oxide in asthma, no studies to date have evaluated levels of plasma arginase or arginine, the substrate for nitric oxide production, in asthmatic patients. This study therefore measured amino acid levels, arginase activity, and nitric oxide metabolites in the blood of asthmatic patients, as well as nitric oxide in exhaled breath. Although levels of virtually all amino acids were reduced, asthmatic patients exhibited a striking reduction in plasma arginine levels compared to non-asthmatic normal controls (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/hr, asthma vs. control, p < 0.0001). High arginase activity in asthmatic patients may contribute to low circulating arginine levels, thereby limiting arginine bioavailability and creating a nitric oxide 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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