BACKGROUND/AIMS: Nitric oxide (NO) is an inhibitory neurotransmitter that's released by the non-adrenergic and non-cholinergic neurons that innervate the smooth muscles of the gastrointestinal tract. However, there was little published data for the effect of isosorbide dinitrate (ISD), a NO donor, on the bolus transit of the esophagus. The aim of this study was to evaluate the effect of an oral spray of ISD on the esophageal function including bolus transit, in healthy volunteers with using combined multichannel intraluminal impedance and esophageal manometry (MII-EM). METHODS: We prospectively performed MII-EM in 8 healthy volunteers. The subjects were given 10 swallows of 5 ml liquid and then 5 ml of viscous material each at 20~30 seconds apart with the subjects in the standing position. These swallows were repeated 5 minutes after an oral spray (3.75 mg) of ISD. RESULTS: The resting pressure of the LES was significantly decreased after an oral spray of ISD (mean+/-SD, 23.8+/-15.1 mmHg vs. 13.0+/-6.5 mmHg, respectively, p<0.05). The duration of the LES relaxation was significantly prolonged (p<0.05). The Viscous-Compete Bolus Transit (CBT) was significantly decreased, but not the liquid-CBT (p<0.01). There were no changes in the degree of peristalsis, the conduction velocity and in the UES pressure and contraction. CONCLUSIONS: The oral spray of ISD significantly decreased viscous bolus transit, but not the liquid bolus transit in the esophagus.