Harm Maarsingh, John Leusink, I Sophie T Bos, Johan Zaagsma, Herman Meurs
Index: Respir. Res. 7 , 6, (2006)
Full Text: HTML
Using guinea pig tracheal preparations, we have recently shown that endogenous arginase activity attenuates inhibitory nonadrenergic noncholinergic (iNANC) nerve-mediated airway smooth muscle relaxation by reducing nitric oxide (NO) production--due to competition with neuronal NO-synthase (nNOS) for the common substrate, L-arginine. Furthermore, in a guinea pig model of allergic asthma, airway arginase activity is markedly increased after the early asthmatic reaction (EAR), leading to deficiency of agonist-induced, epithelium-derived NO and subsequent airway hyperreactivity. In this study, we investigated whether increased arginase activity after the EAR affects iNANC nerve-derived NO production and airway smooth muscle relaxation.Electrical field stimulation (EFS; 150 mA, 4 ms, 4 s, 0.5-16 Hz)-induced relaxation was measured in tracheal open-ring preparations precontracted to 30% with histamine in the presence of 1 microM atropine and 3 microM indomethacin. The contribution of NO to EFS-induced relaxation was assessed by the nonselective NOS inhibitor Nomega-nitro-L-arginine (L-NNA, 100 microM), while the involvement of arginase activity in the regulation of EFS-induced NO production and relaxation was investigated by the effect of the specific arginase inhibitor Nomega-hydroxy-nor-L-arginine (nor-NOHA, 10 microM). Furthermore, the role of substrate availability to nNOS was measured in the presence of exogenous L-arginine (5.0 mM).At 6 h after ovalbumin-challenge (after the EAR), EFS-induced relaxation (ranging from 3.2 +/- 1.1% at 0.5 Hz to 58.5 +/- 2.2% at 16 Hz) was significantly decreased compared to unchallenged controls (7.1 +/- 0.8% to 75.8 +/- 0.7%; P < 0.05 all). In contrast to unchallenged controls, the NOS inhibitor L-NNA did not affect EFS-induced relaxation after allergen challenge, indicating that NO deficiency underlies the impaired relaxation. Remarkably, the specific arginase inhibitor nor-NOHA normalized the impaired relaxation to unchallenged control (P < 0.05 all), which effect was inhibited by L-NNA (P < 0.01 all). Moreover, the effect of nor-NOHA was mimicked by exogenous L-arginine.The results clearly demonstrate that increased arginase activity after the allergen-induced EAR contributes to a deficiency of iNANC nerve-derived NO and decreased airway smooth muscle relaxation, presumably via increased substrate competition with nNOS.
Structure | Name/CAS No. | Molecular Formula | Articles |
---|---|---|---|
![]() |
(-)-isoproterenol hydrochloride
CAS:5984-95-2 |
C11H18ClNO3 |
β-adrenergic receptor-dependent alterations in murine cardia...
2014-01-01 [PLoS ONE 9(6) , e99195, (2014)] |
Thermogenic activity of UCP1 in human white fat-derived beig...
2015-01-01 [Mol. Endocrinol. 29(1) , 130-9, (2014)] |
Alteration of vascular reactivity in heart failure: role of ...
2014-12-01 [Br. J. Pharmacol. 171(23) , 5361-75, (2014)] |
Dynamic mass redistribution reveals diverging importance of ...
2016-03-01 [Pharmacol. Res. 105 , 13-21, (2016)] |
Role of contractile prostaglandins and Rho-kinase in growth ...
2005-01-01 [Respir. Res. 6 , 85, (2005)] |
Home | MSDS/SDS Database Search | Journals | Product Classification | Biologically Active Compounds | Selling Leads | About Us | Disclaimer
Copyright © 2024 ChemSrc All Rights Reserved