Background & Aims: Nitric oxide controls lower esophageal sphincter (L
ES) relaxation and esophageal peristalsis in opossums, but its role in
the control of esophageal motility in humans is not defined. Hemoglob
in inactivates NO by binding it. Recombinant human hemoglobin (rHb1.1)
was used to test the hypothesis that NO mediates esophageal motor fun
ctions in humans. Methods: rHb1.1 or human serum albumin was administe
red intravenously to fasting male volunteers. Esophageal manometric st
udies were performed before, during, and up to 6 hours after the infus
ion. Results: rHb1.1 increased the velocities of peristaltic contracti
ons to produce simultaneous contractions in 6 of 9 subjects. It increa
sed the amplitude and duration of contractile waves in the esophagus.
There was no consistent effect on the resting tone of the LES, but LES
relaxation was inhibited. Spontaneous, simultaneous high-pressure con
tractions occurred in 8 of 9 subjects. Lower retrosternal chest pain d
uring swallowing was observed in 4 subjects. Conclusions: rHb1.1 inter
fered with esophageal peristalsis and LES relaxation. It precipitated
esophageal spasm in some subjects. These data support the hypothesis t
hat the timing of smooth muscle esophageal peristalsis and LES relaxat
ion are mediated by NO. They suggest that some disorders of esophageal
motor function may result from defects in NO neuromuscular communicat
ion.