Sodium sulphide relaxation of rat uterus is related to calcium signaling

Abstract

H2S was shown as an uterine relaxant. However, the signaling pathways, including ion channels regulated by H2S mediating relaxation in uterus are still unknown. The effects on contractility in response to sodium sulphide Na2S were examined on myometrial strips from virgin Wistar rats. Our results showed that Na2S induces concentration-dependent relaxations affecting amplitude as well as frequency of contractions. Activation of potassium channels, and in particular of KATP, was one of the primary mechanisms proposed, responsible for the relaxing effects of H2S. Sodium sulphide (20–200 × 10−6 M) inhibits myometrial contractility through a K-channel-independent mechanism. An inhibitor of 4,4 – inhibitor of Cl-/HCO3- exchanger and/or Cl− channel, DIDS, caused a significant rightward shift of the Na2S concentration–response curve. We performed experiments aimed at different Ca2+ concentrations, using spontaneous, calcium and KCl (15 mM and 75 mM) induced contractions, as well as pharmacological inhibitors of calcium channels and modulators, showing that Na2S induced relaxation is dependent on the precontractile agent used. Taken together, our results suggests that decreased frequency induced by Na2S could be a consequence of a alterated pacemaker cells which might be related for Ca2+ events originates from sarco endoplasmatic reticulum and/or mitochondria.