食塩感受性高血圧に対する脳内アドレノlt;Wュリンの抗酸化作用による中枢性交感神経抑制効果 Sympatho-inhibitory effect of adrenomedullin in the brain on salt-sensitive hypertension through inhibition of oxidative stress

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Author(s)

    • 藤田 恵 Fujita Megumi
    • 東京大学・腎臓内分泌内科|千葉大学・大学院・医学研究院・分子統合生理学 Dept. Nephrology and Endocrinology, Facult. Med., Univ. Tokyo, Tokyo, Japan|Dept. Molecular & Integrative Physiol., Graduate school of Med., Chiba Univ., Chiba, Japan
    • 桑木 共之 Kuwaki Tomoyuki
    • 千葉大学・大学院・医学研究院・分子統合生理学 Dept. Molecular & Integrative Physiol., Graduate school of Med., Chiba Univ., Chiba, Japan

Abstract

Central sympathetic activation is one of the mechanisms of salt-sensitive hypertension and reactive oxygen species (ROS) has been proposed to play a key role in it. We examined whether adrenomedullin (AM), an antioxidant peptide, might contribute to the central regulation of arterial pressure (AP). Four groups of mice were used: AM-knockout mice (AM(+/-)) and wild-type littermates (AM(+/+)), which were fed with normal or high salt diet. In urethane-anesthetized mice, intracerebroventricular infusion of NaCl increased AP and sympathetic nerve activity (SNA) in a dose-dependent fashion. The elevation of AP and SNA in salt-loaded AM(+/-) was significantly greater than those in the other three groups (p<0.05). In freely moving mice, similar exaggerated hypertension was observed in salt-loaded AM(+/-). Pretreatment with a membrane-permeable superoxide dismutase mimetic, Tempol, completely blocked the responses in both AP and SNA, indicating participation of ROS. NaCl-induced ROS production in the hypothalamus was significantly greater in salt-loaded AM(+/-) than in AM(+/+), as determined by chemiluminescence assay. AM contents in the brain from AM(+/+) mice were significantly elevated by salt loading, whereas they were not elevated in AM(+/-) mice. These results suggest that AM in the brain inhibits sympathetic activation in salt-induced hypertension through its antioxidant effect. <b>[Jpn J Physiol 54 Suppl:S99 (2004)]</b>

Central sympathetic activation is one of the mechanisms of salt-sensitive hypertension and reactive oxygen species (ROS) has been proposed to play a key role in it. We examined whether adrenomedullin (AM), an antioxidant peptide, might contribute to the central regulation of arterial pressure (AP). Four groups of mice were used: AM-knockout mice (AM(+/-)) and wild-type littermates (AM(+/+)), which were fed with normal or high salt diet. In urethane-anesthetized mice, intracerebroventricular infusion of NaCl increased AP and sympathetic nerve activity (SNA) in a dose-dependent fashion. The elevation of AP and SNA in salt-loaded AM(+/-) was significantly greater than those in the other three groups (p<0.05). In freely moving mice, similar exaggerated hypertension was observed in salt-loaded AM(+/-). Pretreatment with a membrane-permeable superoxide dismutase mimetic, Tempol, completely blocked the responses in both AP and SNA, indicating participation of ROS. NaCl-induced ROS production in the hypothalamus was significantly greater in salt-loaded AM(+/-) than in AM(+/+), as determined by chemiluminescence assay. AM contents in the brain from AM(+/+) mice were significantly elevated by salt loading, whereas they were not elevated in AM(+/-) mice. These results suggest that AM in the brain inhibits sympathetic activation in salt-induced hypertension through its antioxidant effect. <b>[Jpn J Physiol 54 Suppl:S99 (2004)]</b>

Journal

  • Proceedings of Annual Meeting of the Physiological Society of Japan

    Proceedings of Annual Meeting of the Physiological Society of Japan 2004(0), S99-S99, 2004

    PHYSIOLOGICAL SOCIETY OF JAPAN

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