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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概要
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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-Savilles 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.
著者
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Kawada Tomie
Department of Clinical Pharmacy, Faculty of Pharmacy, Musashino University
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Ishibashi Takaharu
金沢医科大学 看護学部薬理学
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Ishibashi Takaharu
Pharmacology School Of Nursing Kanazawa Medical University:department Of Pharmacology School Of Medi
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Ishii Takashi
Department Of Pharmacology Kanazawa Medical University
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Ishibashi Takaharu
旭川医科大学 薬理
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MIWA Tomoko
Department of Pharmacology, School of Medicine, Kanazawa Medical University
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SHINKAWA Ikumi
Department of Pharmacology, School of Medicine, Kanazawa Medical University
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Yoshida Junko
Department Of Obstetrics And Gynecology Shinshu University School Of Medicine
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Miwa Tomoko
Department Of Pharmacology School Of Medicine Kanazawa Medical University
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Shinkawa Ikumi
Department Of Pharmacology School Of Medicine Kanazawa Medical University
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Nishizawa Naoki
Department Of Medicinal Chemistry Kyoto Pharmaceutical University
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Ishibashi Takaharu
Department Of Pharmacology Asahikawa Medical College
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Nishio Matomo
Department Of Endocrinology Kanazawa Medical University
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KAWADA Tomie
Department of Clinical Pharmacology, Faculty of Pharmacy, Musashino University
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Nishio Matomo
Department of Pharmacology, School of Medicine, Kanazawa Medical University
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