title: 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 (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 ETAreceptor 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 ETAreceptor upregulation, which may be associated with MAPK signal pathways. H2S ameliorates endothelial-dependent relaxation, which may be through antioxidant activity.
authors: Department of Pharmacology, Xi'an Jiaotong University College of Medicine, 76 Yanta West Road, Xi'an, 710061, Shannxi, China.|Shaanxi Blood Center, Xi'an, 710061, Shannxi, China.
authors: Na-Na
authors: NN
authors: Ping
authors: Department of Pharmacology, Xi'an Jiaotong University College of Medicine, 76 Yanta West Road, Xi'an, 710061, Shannxi, China.
authors: Yan-Ni
authors: YN
authors: Mi
authors: Department of Pharmacology, Xi'an Jiaotong University College of Medicine, 76 Yanta West Road, Xi'an, 710061, Shannxi, China.
authors: Dong-Zheng
authors: DZ
authors: Liu
authors: Department of Pharmacology, Xi'an Jiaotong University College of Medicine, 76 Yanta West Road, Xi'an, 710061, Shannxi, China.
authors: Sai
authors: S
authors: Zhang
authors: Department of Pharmacology, Xi'an Jiaotong University College of Medicine, 76 Yanta West Road, Xi'an, 710061, Shannxi, China.
authors: Jing-Guo
authors: JG
authors: Chen
authors: Department of Pharmacology, Xi'an Jiaotong University College of Medicine, 76 Yanta West Road, Xi'an, 710061, Shannxi, China. yxy@mail.xjtu.edu.cn.
authors: Yong-Xiao
authors: YX
authors: Cao
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D016572:Cyclosporine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014666:Vasomotor System / Q000187:drug effects* / Q000502:physiology
chemical_list: D000935:Antifungal Agents; D016572:Cyclosporine; D006862:Hydrogen Sulfide
keywords: Antioxidant; Cyclosporine A; Hydrogen sulfide; Hypertension; Vascular dysfunction