Diethylenetriamine NITRIC oxide adduct relaxes precontracted mouse tracheal smooth muscle

Authors: Lam C.F.; Lan R.S.; van Heerden P.V.; Ilett K.F.; Henry P.J.

Source: Clinical and Experimental Pharmacology and Physiology, Volume 30, Number 9, September 2003 , pp. 709-711(3)

Publisher: Wiley-Blackwell

Abstract:

Summary

1. Inhaled diethylenetriamine nitric oxide adduct (DETA/NO) has been shown to be a selective pulmonary vasodilator in animal and human studies. The aims of the present study were to investigate the effect of DETA/NO on mouse precontracted isolated tracheal smooth muscle preparations and to determine the active component of this compound.

2. Mouse isolated tracheal smooth muscle rings were precontracted with carbachol (10^-7 mol/L). Changes in isometric tension were recorded after cumulative addition of DETA (30–300 µmol/L; n = 6), DETA/NO (30–300 µmol/L; n = 9) or diluent control (n = 3). In addition, some preparations (n = 5) were pretreated with the soluble guanylyl cyclase (sGC) inhibitor 1H-[1,2,4]-oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ; 30 µmol/L) before precontraction and exposure to DETA/NO.

3. Addition of DETA/NO caused a concentration-dependent relaxation of tracheal smooth muscle at 100 and 300 µmol/L, with an EC_25%R of 109 µmol/L (95% confidence interval 72.6–164 µmol/L). The nucleophile amine carrier DETA had no effect on isometric tension. However, the relaxant effect of DETA/NO was completely abolished by pretreatment with ODQ.

4. We conclude that DETA/NO induces a concentration-dependent relaxation of mouse carbachol-contracted isolated tracheal smooth muscle that is mediated by NO released from DETA/NO via the activation of sGC.

Keywords: diethylenetriamine nitric oxide adduct; nitric oxide; soluble guanylyl cyclase; trachea

Document Type: Short communication

DOI: http://dx.doi.org/10.1046/j.1440-1681.2003.03889.x

Affiliations: 1: Pharmacology Unit, School of Medicine and Pharmacology, University of Western Australia, Crawley and

Publication date: 2003-09-01

Related content

• In this: publication
• By this: publisher
• In this Subject: Pharmacology
• By this author: Lam C.F. ;  Lan R.S. ;  van Heerden P.V. ;  Ilett K.F. ;  Henry P.J.

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers