Nitric oxide in the mechanisms of inhibitory effects of sodium butyrate on colon contractions in a mouse model of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a multifactorial disorder, with altered intestinal motility, visceral hypersensitivity, and dysfunction of the gut-brain axis. The aim of our study was to analyze the role of nitric oxide (NO) in the inhibitory effects of sodium butyrate on spontaneous contractility of proximal colon in a mouse model of IBS. IBS was induced by intracolonic infusion of acetic acid in the early postnatal period. Spontaneous contractions of proximal colon segments were studied in isometric conditions. The amplitude and frequency of colon contractions were higher in the IBS group. Sodium butyrate exerted inhibitory effects on colon contractions, which were less pronounced in IBS group. NO donors decreased spontaneous colon contractility and prevented the inhibitory effects of sodium butyrate in control and IBS groups. Nitric oxide synthase (NOS) inhibition by L-NAME increased contractile activity more effective in the control group and decreased the inhibitory action of sodium butyrate. In IBS group, preliminary application of L-NAME did not prevent sodium butyrate action. Our data indicate that butyrate exerts its inhibitory effects on colon motility at least partially through activation of NO synthesis. In the IBS model group, the NO-dependent mechanisms were less effective probably due to downregulation of NOS.