Diethylenetriamine nitric oxide adduct relaxes precontracted mouse tracheal smooth muscle.

Abstract

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 micromol/L; n = 6), DETA/NO (30-300 micromol/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 micromol/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 micromol/L, with an EC25%R of 109 micromol/L (95% confidence interval 72.6-164 micromol/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.