Effects of nitric oxide on antral motility and gastric emptying in humans

Abstract

Objective: It has been suggested that nitric oxide is a nonadrenergic-noncholinergic (NANC) inhibitory neurotransmitter released by the nerves in the gastrointestinal tract. We studied the influence of nitric oxide on gastric emptying and antral motility using glyceryl trinitrate (GTN), a donor of nitric oxide and L-arginine as the substrate of nitric oxide synthase.

Design: Six male volunteers (aged 21-24 years) participated in this placebo-controlled, double-blind study.

Methods: We investigated the effects of 0.8 mg sublingual GTN, 300 mg/kg/h intravenous L-arginine or placebo on meal-stimulated antral motility and gastric emptying on four separate occasions. After an overnight fast, a 500 ml standard liquid meal was ingested and the gastric emptying rate assessed by ultrasound. The changes in antral cross-sectional areas were measured by ultrasonography and the antral motor activity was determined simultaneously using a multilumen perfused catheter. Blood samples were taken from fasted and fed patients before and after the administration of GTN, L-arginine or placebo to determine plasma glucagon and somatostatin levels.

Results: GTN at a sublingual dose of 0.8 mg and 300 mg/kg/h intravenous L-arginine significantly (P < 0.01) prolonged gastric emptying half-time, averaging 56 +/- 12 and 38 +/- 8 min, respectively, compared with the placebo control value (28 +/- 7 min). The antral motor activity, calculated as the motility index (number of contractions x mmHg/min) significantly decreased in both test series, i.e., after GTN from 375.5 +/- 185.1 (control) to 104.4 +/- 55.7 (P < 0.01) and after L-arginine from 401 +/- 76 (control) to 285 +/- 57 (P < 0.05). L-arginine given intravenously at a dose of 300 mg/kg/h significantly increased plasma glucagon and somatostatin in fasted patients and increased postprandially released glucagon without affecting postprandial plasma somatostatin levels. GTN did not affect plasma hormone levels.

Conclusions: Our results indicate that (1) exogenous nitric oxide inhibits gastric emptying and antral motor activity, which could be useful in the treatment of patients with functional disturbances of gastric motility and emptying; and (2) the reduction in gastric emptying and antral motility observed after the administration of L-arginine results from changes in plasma enterohormone release rather than from the enhanced formation of endogenous nitric oxide.