Comparison of Relaxation Induced by Glyceryl Trinitrate, Isosorbide Dinitrate, and Sodium Nitroprusside in Bovine Airways

Nitrates are generally regarded as bronchial smooth muscle relaxants. However, reports about the clinical efficacy of the nitrates in the treatment of asthma are conflicting. In the present study, the relaxant effects of glyceryl trinitrate, isosorbide dinitrate, sodium nitroprusside, and isoproterenol were measured and compared in vitro in airway preparations isolated from variously sized airways in bovine lung. Strips of trachealis from cervical and thoracic ends of the trachea and rings of intrapulmonary bronchi of various diameters (14 to 1 mm outer diameters) were mounted for recording of isometric tension. Submaximal tone was induced using 10−6 M carbachol, and responses to cumulatively increasing concentrations of glyceryl trinitrate, isosorbide dinitrate, sodium nitroprusside, or isoproterenol were measured. Isoproterenol (10−8 to 10−4 M) was equiactive as a relaxant in all preparations. Glyceryl trinitrate (10−7 to 10−5 M) relaxed trachealis, but was progressively and significantly less effective as a relaxant as the diameters of the bronchial rings decreased. Although less potent than isoproterenol, sodium nitroprusside (10−6 to 10−4 M) was effective in relaxing all the airway preparations. Similar to glyceryl trinitrate, sodium nitroprusside was less effective in small than in large airways. However, the relationship between relaxant responses to sodium nitroprusside and airway size was not as marked as for glyceryl trinitrate. Isosorbide dinitrate at concentrations as great as 10−5 M did not relax carbachol-induced tone in any of the bronchial rings and only induced a small amount of relaxation in trachealis at 10−5 M. The results demonstrate that, in contrast to relaxation induced by isoproterenol, responsiveness of bovine airways to glyceryl trinitrate, and to a lesser extent to sodium nitroprusside, varies depending upon the site in the tracheobronchial tree from which it is isolated. Isosorbide dinitrate was minimally effective as a relaxant of bovine airway smooth muscle at the concentrations used in the study.