Effects of 3‐days' intake of a sustained‐release preparation of the nitric oxide donor, isosorbide dinitrate, on oesophageal motility

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Abstract
Background: Nitric oxide plays an important role in gastrointestinal motility. We evaluated the effects of a sustained‐release preparation of the nitric oxide donor isosorbide dinitrate on swallow‐initiated oesophageal contractions and the lower oesophageal sphincter. Methods: Twelve healthy men, aged 23–32 years, received, at 1‐week intervals and under random double‐blind conditions, for 3 days either 20 mg isosorbide dinitrate, 40 mg isosorbide dinitrate or placebo twice daily (b.d.). One hour after a further dose on day 4, oesophageal motility was recorded for 30 min using a multilumen catheter with a Dent sleeve straddling the lower oesophageal sphincter and side‐hole openings 0, 3, 6 and 9 cm proximal to the sleeve. Contractile responses to twelve 5‐mL water swallows were evaluated. Results: Amplitude, duration, propagation velocity and onset latency of oesophageal contractions were not affected by either dosage of isosorbide dinitrate. Lower oesophageal sphincter resting pressure was significantly lower after 40 mg (15.1 mmHg ± 1.2 S.E.M.) and 20 mg isosorbide dinitrate b.d. (15.0 ± 1.0 mmHg) than after placebo (17.9 ± 1.7 mmHg; P<0.025). Headache was reported by all subjects on 40 mg isosorbide dinitrate, seven subjects on 20 mg and by one on placebo. Conclusions: Twenty and 40 mg sustained‐release isosorbide dinitrate twice daily had no effect on swallow‐initiated oesophageal contractions but decreased lower oesophageal sphincter resting pressure.

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