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Diethylenetriamine NITRIC oxide adduct relaxes precontracted mouse tracheal smooth muscle *
Author(s) -
Lam Chen Fuh,
Lan Rommel S,
Van Heerden Peter V,
Ilett Kenneth F,
Henry Peter J
Publication year - 2003
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2003.03889.x
Subject(s) - carbachol , diethylenetriamine , nitric oxide , chemistry , soluble guanylyl cyclase , muscle relaxation , vasodilation , endocrinology , medicine , biochemistry , guanylate cyclase , receptor , organic chemistry
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.