US EPA

2263258 

Journal Article 

Abstract 

Role of nitric oxide and arginase on muscarinic-induced contractility in isolated trachea of non-challenged and allergen-challenged Brown Norway rat 

Corboz, MR; Rivelli, MA; Phillips, JE; Chapman, RW; Anthes, J 

2010 

Yes 

American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 

181 

A2833 

English 

10.1164/ajrccm-conference.2010.181.1_MeetingAbstracts.A2833 

WOS:000208771001745 

is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans

Endogenous nitric oxide (NO) produced by nitric oxide synthase (NOS) isoforms, plays a major role in the regulation of airway tone by inducing relaxation of airway smooth muscle. A deficiency of the bronchodilator NO contributes to airway hyperreactivity in inflammatory conditions and one possible mechanism is the reduced bioavailability of the amino acid L-arginine due to enhanced arginase activity. Indeed, L-arginine is a substrate for NOS and arginase and the availability of L-arginine to NOS is regulated by substrate competition between NOS and arginase. Previous reports in human and animal models have indicated that L-arginine metabolism is altered in asthma through expression and activity of arginase. This study was therefore undertaken to determine whether NO and arginase exert a significant role in isolated trachea from ovalbumin (OVA) challenged Brown Norway rat. Tracheae were collected from Brown Norway rats 48 hours after saline or OVA challenge. Trachea rings (1.5 - 2.0 mm internal diameter) were then placed in a 25 ml organ bath filled with Krebs-Ringer solution maintained at 37°C and aerated with 95%O2 - 5%CO2 and attached to force displacement transducers for continuous recording of isometric tension. In the first set of experiments, the muscarinic agonist carbachol (10^-7 - 10^-3 M) produced dose-dependent contractions in isolated trachea from non-challenged animals similar to the ones from OVA challenged Brown Norway rats. Pretreatment with the arginase inhibitor ABH (10^-4 M) had no effect on the dose-response to carbachol in isolated trachea from non-challenged and OVA challenged Brown Norway rats. In a second set of experiments, addition of L-arginine (10^-6 - 10^-3 M) in isolated tracheas pre-contracted with a submaximal dose of carbachol (10^-6 M) produced significant relaxation in non-challenged animals while a smaller dose-dependent relaxation was observed in carbachol pre-contracted trachea from OVA challenged Brown Norway rat. The arginase inhibitor ABH (10^-7 - 10^-4 M) did not affect tracheal tone in carbachol pre-contracted tissues from non-challenged and OVA challenged animals. However, standard bronchodilator agents such as the b2-adrenoceptor agonist albuterol (10^-8 - 10^-4M) and the PDE4 inhibitor roflumilast (10^-8 - 10^-4 M) dose-dependently relaxed carbachol pre-contracted isolated tracheae. These results suggest that arginase inhibition does not relax tracheal tone through the classical bronchodilator pathways in the Brown Norway rat preparation. The isolated Brown Norway rat trachea is not the appropriate preparation for airway hyperreactivity and consequently assessment of arginase activity. 

American Thoracic Society 2010 International Conference 

New Orleans, LA 

May 14-19, 2010