Abstract

Background and aims: Impaired accommodation and hypersensitivity to distension of the proximal stomach are considered to be important factors in the pathogenesis of dyspeptic complaints. As fundus relaxing agents may be effective in the treatment of these symptoms, insight into the mediators involved in fundic accommodation and associated perceptual responses is important. Therefore, we studied the effect of nitric oxide (NO) synthase inhibition by N^G-monomethyl-l-arginine (l-NMMA) on fundic tone, postprandial sensations, and gastric perception in healthy volunteers.

Subjects and methods: Eighteen healthy volunteers participated in a double blind, placebo controlled, randomised study. They underwent a gastric barostat study to evaluate the effect of l-NMMA on meal and distension induced sensations and on fundic relaxation in response to oral meal intake, intraduodenal lipid, and glucagon administration.

Results: Compared with placebo, l-NMMA decreased fundic volume after oral meal intake (438 (55) v 304 (67) ml; n=8; p<0.05) and during intraduodenal lipid infusion (384 (37) v 257 (43) ml; n=10; p<0.05) but not after glucagon injection (570 (62) v 540 (52) ml; n=4; p=0.4). In addition, basal fundic volume was significantly reduced by l-NMMA. Scores for nausea and satiation were decreased by l-NMMA after oral meal intake but not during intraduodenal lipid infusion. Perception scores to gastric distension were not altered by l-NMMA.

Conclusions: NO is involved in maintaining basal fundic tone and in meal induced fundic relaxation in humans, but not in visceral perception.