H2S Prevents Cyclosporine A-Induced Vasomotor Alteration in Rats

Autor: Sai Zhang, Na-na Ping, Yong-Xiao Cao, Yan-ni Mi, Dong-Zheng Liu, Jingguo Chen
Rok vydání: 2016
Předmět:
Zdroj: Cardiovascular Toxicology. 17:287-296
ISSN: 1559-0259
1530-7905
DOI: 10.1007/s12012-016-9383-x
Popis: 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 (ETA) 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 ETA 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 ETA receptor upregulation, which may be associated with MAPK signal pathways. H2S ameliorates endothelial-dependent relaxation, which may be through antioxidant activity.
Databáze: OpenAIRE
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