Effects of Hydrogen Sulfide and Nitric Oxide on Rat Jejunum Contractions in a Model of Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a functional, multifactorial disorder of the gastrointestinal tract characterized by intestinal dysmotility and visceral hypersensitivity. The aim of the study was to analyze the effects of H2S and NO on spontaneous contractions of the jejunum in a rat model of IBS. IBS was induced by neonatal maternal deprivation and verified by the assessment of visceral hypersensitivity. Spontaneous contractions of the isolated rat jejunum preparation were recorded under isometric conditions. In rats with IBS, the amplitude of jejunal spontaneous contractions and preparation tone were lower than in the control group, with no changes in the frequency of spontaneous contractions. The H2S donor, sodium hydrosulfide (NaHS), exerted an inhibitory effect on jejunal contractions in the control, whereas in the IBS group, this effect of NaHS was not manifested. The NO donor, sodium nitroprusside (SNP), caused amplitude inhibition in both groups, while reducing the inhibitory effect of NaHS in the control group. The nitric oxide synthase (NOS) inhibitor, L-NAME, led to an increase in the amplitude of spontaneous contractions in both groups, with more pronounced effects in the IBS group. Under conditions of NOS blockade, the inhibitory action of NaHS on the amplitude of spontaneous contractions was restored in the IBS group. In the same group, the expression of cystathionine-β-synthase (CBS), as well as the sulfide level and the activity of H2S-synthesizing enzymes, in the rat jejunal tissues were lower, whereas the expression of neuronal NOS and the concentration of NO metabolites were elevated compared to the control. The obtained data suggest that in IBS, due to excessive NO synthesis, changes occur in the activity of CBS, as well as signaling pathways and/or targets of H2S action, leading to jejunal dysmotility and causing the symptoms of increased peristalsis in diarrhea-predominant IBS (IBS-D).