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  • 标题:Role of Plasma S-Nitrosothiols in Regulation of Blood Pressure in Anesthetized Rabbits with Special References to Hypotensive Effects of Acetylcholine and Nitrovasodilators
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  • 作者:Takaharu Ishibashi ; Tomoko Miwa ; Naoki Nishizawa
  • 期刊名称:Biological and Pharmaceutical Bulletin
  • 印刷版ISSN:0918-6158
  • 电子版ISSN:1347-5215
  • 出版年度:2011
  • 卷号:34
  • 期号:8
  • 页码:1307-1313
  • DOI:10.1248/bpb.34.1307
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:The regulatory role of plasma nitrosothiols (R-SNOs) under steady-state conditions and their possible contribution to pharmacological vasodilation were systematically examined in anesthetized rabbits. Nitrosocystein (Cys-NO), S -nitrosoglutathione (G-SNO), and S -nitrosoalbumin (Alb-SNO) were determined by HPLC-Saville's method with respective sensitivities of 1, 1, and 5 n M . These R-SNOs were not detected under steady-state conditions even in the presence of N -ethylmaleimide, a thiol protective agent used to prevent transnitrosation of R-SNOs. Development of plasma Alb-SNO below 300 n M was observed after intravenous injection (i.v.) of nitric oxide (NO) solution (0.1 to 3 ml/g), NOC7 (an NO releasing agent, above 1 μg/kg), and a low dose of Alb-SNO (10 nmol/kg). However, blood pressure was not significantly reduced by NO solution or Alb-SNO. Intravenous injection of a high dose of Alb-SNO (300 nmol/kg) significantly reduced blood pressure with the appearance not only Alb-SNO in micromolar level in plasma, but also G-SNO in lesser degree. Conversely, the hypotensive effect of Cys-NO (300 nmol/kg, i.v.) and G-SNO (300 nmol/kg, i.v.) accompanied development of Alb-SNO (micromolar level), but not Cys-NO or G-SNO in plasma. R-SNOs were not found in plasma during profound hypotension induced by acetylcholine (10 and 30 μg/kg/min, continuous i.v.), glyceryl trinitrate (100 μg/kg, i.v.), sodium nitroprusside (100 μg/kg, i.v.), and isosorbide dinitrate (300 μg/kg, i.v.). These results indicate that R-SNOs do not play an important role under unstimulated condition. In addition, plasma R-SNOs may not be involved in pharmacological vasodilation where contributions of NO or R-SNOs are suggested.
  • 关键词:nitrosothiol;rabbit;acetylcholine;glyceryl trinitrate;sodium nitroprusside;isosorbide dinitrate
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