Diethylenetriamine Nitric Oxide Adduct Relaxes Precontracted Mouse Tracheal Smooth Muscle

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