Abstract <p>Irritable bowel syndrome (IBS) is a functional, multifactorialdisorder of the gastrointestinal tract characterized by intestinaldysmotility and visceral hypersensitivity. The aim of the studywas to analyze the effects of H₂S and NOon spontaneous contractions of the jejunum in a rat model of IBS.IBS was induced by neonatal maternal deprivation and verified bythe assessment of visceral hypersensitivity. Spontaneous contractionsof the isolated rat jejunum preparation were recorded under isometric conditions.In rats with IBS, the amplitude of jejunal spontaneous contractionsand preparation tone were lower than in the control group, withno changes in the frequency of spontaneous contractions. The H₂Sdonor, sodium hydrosulfide (NaHS), exerted an inhibitory effecton 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 reducingthe inhibitory effect of NaHS in the control group. The nitric oxidesynthase (NOS) inhibitor, L-NAME, led to an increase in the amplitudeof spontaneous contractions in both groups, with more pronouncedeffects in the IBS group. Under conditions of NOS blockade, theinhibitory action of NaHS on the amplitude of spontaneous contractionswas restored in the IBS group. In the same group, the expressionof cystathionine-β-synthase (CBS), as well as the sulfide leveland the activity of H₂S-synthesizing enzymes,in the rat jejunal tissues were lower, whereas the expression ofneuronal NOS and the concentration of NO metabolites were elevatedcompared to the control. The obtained data suggest that in IBS,due to excessive NO synthesis, changes occur in the activity ofCBS, as well as signaling pathways and/or targets of H₂Saction, leading to jejunal dysmotility and causing the symptomsof increased peristalsis in diarrhea-predominant IBS (IBS-D).</p>