H2S Prevents Cyclosporine A-Induced Vasomotor Alteration in Rats

Abstract

Cyclosporine A (CsA) induces hypertension after transplantation. Hydrogen sulfide (H₂S) was found to have hypotensive/vasoprotective effects in the cardiovascular system. The present study aims to investigate the role of H₂S 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_A) 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 H₂S donor, significantly attenuated the increase of blood pressure and contractile responses, and the upregulation of ET_A 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, H₂S prevents CsA-induced vasomotor dysfunction. H₂S attenuates CsA-induced ET_A receptor upregulation, which may be associated with MAPK signal pathways. H₂S ameliorates endothelial-dependent relaxation, which may be through antioxidant activity.

Keywords: Antioxidant; Cyclosporine A; Hydrogen sulfide; Hypertension; Vascular dysfunction.