The anti-thrombotic effect of hydrogen sulfide is partly mediated by an upregulation of nitric oxide synthases

Introduction Hydrogen sulfide (H 2 S) known as a gasotransmitter is increasingly recognized for its anti-adhesive, anti-inflammatory and vasoactive properties. Due to these properties, we analysed anti-thrombotic effects of H 2 S and the participation of the nitric oxide synthase (NOS)-pathway. Materials and Methods In individual venules of the ear of hairless SKH1-hr mice, thrombus formation was induced using a phototoxic light/dye-injury model and intravital fluorescence microscopy. Animals were treated intravenously with the H 2 S donor Na 2 S or NaCl as control. In a second setting, the NOS inhibitor L-NAME was applied intraperitoneally as a bolus 12 h prior to Na 2 S treatment and thrombus induction. Blood and ear tissue were sampled after microscopy for assessment of plasma concentrations of soluble (s)P-selectin, sE-selectin, sVCAM-1 and sICAM-1 and expression of endothelial (e)NOS and inducible (i)NOS, respectively. Results When mice were treated with Na 2 S, venular thrombus formation was significantly delayed versus that in animals of the NaCl-treated control group. While plasma levels of pro-thrombotic adhesion molecules were not affected by Na 2 S, immunohistochemistry of the vessel walls showed a significant up-regulation of eNOS and iNOS expression within the Na 2 S-treated group. The delay of thrombus formation in the Na 2 S-group was partly but significantly reverted by application of L-NAME. Conclusions The anti-thrombotic efficacy of H 2 S involves the NOS-pathway and may be of preventive and therapeutic value for clinical disorders with increased risk of thrombotic events.