Effect of the nitric oxide donor, glyceryl trinitrate, on human gall bladder motility

Abstract

Background: Nitric oxide is a major neurotransmitter in non-adrenergic, non-cholinergic (NANC) pathways. NANC inhibitory innervation has been shown in human gall bladder muscle in vitro; the role of nitric oxide in human gall bladder emptying however is undefined.

Aims: To study the effect of glyceryl trinitrate, a nitric oxide donor, on gall bladder emptying in healthy subjects using a randomised, double blind, cross-over, placebo controlled design.

Methods: Ultrasonographic gall bladder volume was measured in the fasting state in eight healthy volunteers after randomised administration of either glyceryl trinitrate 1200 micrograms buccal spray or placebo spray. On two further occasions, after randomised administration of either glyceryl trinitrate 1200 micrograms buccal spray or placebo spray, gall bladder volumes were also measured after a liquid test meal.

Results: Glyceryl trinitrate significantly increased fasting gall bladder volume to a mean of 114% (SEM 5%) of pretreatment volume (p = 0.039). Glyceryl trinitrate also significantly impaired gall bladder emptying between five and 40 minutes postprandially. Gall bladder ejection fraction was also reduced after glyceryl trinitrate compared with placebo (43 (6.9)% versus 68.4 (6.5)%, p = 0.016).

Conclusions: This study shows that glyceryl trinitrate produces gall bladder dilatation in the fasting state and reduces postprandial gall bladder emptying, suggesting that nitric oxide mechanisms may be operative in the human gall bladder in vivo.

Figure 1

Effect of GTN 1200 µg buccal spray or placebo on the time course of gall bladder emptying following a liquid test meal in healthy subjects, expressed as percentage of control fasting volume. Results are expressed as mean (SEM). *p<0.05.

Figure 2

Gall bladder ejection fraction following a liquid test meal with either GTN 1200 µg or placebo. The solid horizontal bars represent the mean values. *p<0.05.