Intestinal nitric oxide output during reduced mucosal blood flow in healthy volunteers.
OBJECTIVE
Nitric oxide regulates epithelial permeability and other properties of the intestinal mucosal barrier. It previously has been shown in animals that intestinal mucosal nitric oxide production is impaired during gut hypoperfusion. The study was performed to confirm the presence of intestinal mucosal nitric oxide production in humans and to investigate the effect of gut hypoperfusion due to moderate arterial hypotension on intestinal nitric oxide concentrations.


METHODS
Open study where each subject served as his own control.


METHODS
Clinical research laboratory.


METHODS
Nine healthy volunteers were intubated with a nasogastrointestinal tube for recordings in the distal duodenum. Intestinal nitric oxide output and motility were assessed by tonometry and manometry, respectively. Laser Doppler flowmetry and plasma angiotensin II concentration were used to investigate mucosal perfusion and a vasoregulatory response.


METHODS
Moderate hypotension was induced with lower body negative pressure over 1 hr.


RESULTS
Intestinal nitric oxide production varied in parallel with the migrating motor complex. Low values were obtained during phase I and peak values during phase III. Lower body negative pressure was initiated at a well-defined point in the migrating motor complex cycle. It was followed by a 40 +/- 6% reduction of laser Doppler flow signal, a 778 +/- 138% increase in angiotensin II, and a reduction in intestinal mucosal nitric oxide production by 48 +/- 8%. After lower body negative pressure, laser Doppler signal and angiotensin II concentrations returned to baseline levels within 1 hr, whereas intestinal nitric oxide output remained decreased.


CONCLUSIONS
Intestinal tonometry in humans exhibits a considerable mucosal nitric oxide formation that varies in relation to intestinal motility. Intestinal nitric oxide production is depressed during conditions with lowered mucosal blood perfusion.
Snygg
Johan
J
Department of Anaesthesiology and Intensive Care, Sahlgrens University Hospital, Göteborg, Sweden. johan.snygg@vgregion.se
Aneman
Anders
A
Pettersson
Anders
A
Fändriks
Lars
L
D000328:Adult; D000804:Angiotensin II / Q000097:blood; D004386:Duodenum / Q000098:blood supply / Q000378:metabolism*; D005769:Gastrointestinal Motility; D006439:Hemodynamics; D006801:Humans; D007413:Intestinal Mucosa / Q000098:blood supply / Q000378:metabolism*; D007441:Intubation, Gastrointestinal; D017078:Laser-Doppler Flowmetry; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D012016:Reference Values
D000804:Angiotensin II; D009569:Nitric Oxide