Effect of nebulised l- and d-arginine on exhaled nitric oxide in steroid naive asthma

Abstract

BACKGROUNDNitric oxide (NO) is a product of the enzyme nitric oxide synthase (NOS) and is found in normal and asthmatic human airways. The administration ofl-arginine results in an increase in airway NO production in asthmatic subjects. This is thought to occur becausel-arginine is the substrate for NOS. However, studies in the systemic vasculature suggest that other mechanisms may be responsible.METHODSEight patients with steroid naive asthma each received 2.5 g l-arginine, 2.5 g d-arginine, and 2.0% saline by ultrasonic nebuliser on separate days in a randomised, single blind manner. Exhaled NO was measured by chemiluminescence and spirometric tests were performed before and for 3 hours after each administration. The mean concentration of NO after exposure was calculated from the area under the curve.RESULTSl-arginine,d-arginine, and 2.0% saline induced a mean (95% CI) maximal bronchoconstriction of 11.9% (–1.7 to 25.4), 10.0% (2.8 to 17.2), and 8.5% (–2.5 to 19.5) of the starting forced expiratory volume in one second (FEV1), respectively. Exhaled NO declined in proportion to the degree of bronchoconstriction (r=0.60, p<0.01). Bronchoconstriction and the acute reduction in exhaled NO resolved within 15 minutes. The mean post-exposure concentration of NO was 15.75 parts per billion (ppb) after l-arginine, 15.16 ppb after d-arginine, and 12.74 ppb after 2.0% saline. The mean (95% CI) difference between l-arginine and placebo was 3.01 (0.32 to 5.7) ppb, between d-arginine and placebo 2.42 (0.10 to 4.74) ppb, and between l- and d-arginine 0.59 (–1.56 to 2.74) ppb.CONCLUSIONSExhaled NO decreased with acute bronchoconstriction and returned to baseline with the resolution of bronchoconstriction. Exhaled NO increased following the administration of both l-arginine andd-arginine. Since NOS is stereospecific, this finding suggests that the increase in exhaled NO is not entirely mediated through an increase in NOS enzyme activity. We suggest that arginine may react in a non-stereospecific fashion with reactive oxygen species present in asthmatic airways.