title: Role of plasma S-nitrosothiols in regulation of blood pressure in anesthetized rabbits with special references to hypotensive effects of acetylcholine and nitrovasodilators.
abstract: 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 nM. 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 nM 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.
authors.affiliation: Pharmacology, School of Nursing, Kanazawa Medical University, Ishikawa, Japan. ishitaka@kanazawa-med.ac.jp
authors.forename: Takaharu
authors.initials: T
authors.lastname: Ishibashi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Miwa
authors.forename: Naoki
authors.initials: N
authors.lastname: Nishizawa
authors.forename: Ikumi
authors.initials: I
authors.lastname: Shinkawa
authors.forename: Junko
authors.initials: J
authors.lastname: Yoshida
authors.forename: Tomie
authors.initials: T
authors.lastname: Kawada
authors.forename: Matomo
authors.initials: M
authors.lastname: Nishio
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D005033:Ethylmaleimide / Q000494:pharmacology; D007022:Hypotension / Q000097:blood / Q000139:chemically induced*; D009569:Nitric Oxide / Q000494:pharmacology; D011817:Rabbits; D026403:S-Nitrosothiols / Q000097:blood* / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*
chemical_list: D026403:S-Nitrosothiols; D009569:Nitric Oxide; D000109:Acetylcholine; D005033:Ethylmaleimide