Effects of 3-days' intake of a sustained-release preparation of the nitric oxide donor, isosorbide dinitrate, on oesophageal motility.
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.
Stacher
G
G
Department of Surgery, University of Vienna, Austria.
Schneider
C
C
Steinringer
H
H
Holzäpfel
A
A
Gaupmann
G
G
Stacher-Janotta
G
G
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004947:Esophagus / Q000187:drug effects* / Q000502:physiology; D005769:Gastrointestinal Motility; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007548:Isosorbide Dinitrate / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*
D003692:Delayed-Action Preparations; D009569:Nitric Oxide; D007548:Isosorbide Dinitrate