Influence of nitric oxide synthase inhibition on the motility and sensitivity of distal colon in man

Abstract

Alterations of nitrergic innervation have been implicated in the pathophysiology of motor-sensory abnormalities of post infectious functional dyspepsia and could be involved in the pathophysiology of post infectious irritable bowel syndrome. The role of nitrergic neurons in the control of distal colonic sensorimotor function in man is not known. The aim of this study is to evaluate the motility and sensitivity of distal colon in healthy subjects before and after a nitric oxide synthase inhibitor (L-NMMA). A 700-mL balloon connected with a barostat-manometry assembly was placed in the descending colon of 10 healthy subjects and distension (4 mmHg/2 min) was performed. Intra-balloon pressure was then set at minimal distending pressure + 2 mmHg for 30 min, placebo or L-NMMA (8 mg kg(-1) h(-1)) was administered i.v. in double-blind, randomized, cross-over design and distensions were repeated. Placebo and L-NMMA did not influence colonic compliance, motility index, and tone. Placebo did not affect thresholds for first perception and discomfort and the areas under the pressure-perception curve. L-NMMA did not alter thresholds for first perception, but significantly decreased the pressure thresholds for discomfort (P = 0.008) and increased the areas under the pressure-perception score (P = 0.01). In man, inhibition of nitric oxide synthase sensitizes the distal colon to distension. Impaired nitrergic innervation is a mechanism that may be involved in the pathogenesis of hypersensitivity to colonic distension.