HS Prevents Cyclosporine A-Induced Vasomotor Alteration in Rats.

Cyclosporine A (CsA) induces hypertension after transplantation. Hydrogen sulfide (HS) was found to have hypotensive/vasoprotective effects in the cardiovascular system. The present study aims to investigate the role of HS on CsA-induced vascular function disorder in rats. Rats were subcutaneously injected with CsA 25 mg/kg for 21 days. Blood pressure was measured by the tail-cuff method. Vasomotion was determined using a sensitive myograph. Western blotting and immunohistochemistry were used to quantify the protein expression of endothelin type A (ET) receptor and essential MAPK pathway molecules. Vascular superoxide anion production and serum contents of malondialdehyde were determined. The results showed that sodium hydrosulfide (NaHS), a HS donor, significantly attenuated the increase of blood pressure and contractile responses, and the upregulation of ET receptor induced by CsA. In addition, NaHS could restore the CsA decreased acetylcholine-induced vasodilatation. Furthermore, NaHS blocked the CsA-induced elevation of reactive oxygen species level, extracellular signal-regulated kinase and p38 MAPK activities. In conclusion, HS prevents CsA-induced vasomotor dysfunction. HS attenuates CsA-induced ET receptor upregulation, which may be associated with MAPK signal pathways. HS ameliorates endothelial-dependent relaxation, which may be through antioxidant activity.