Reduced growth, abnormal kidney structure, and type 2 (AT <sub>2</sub> ) angiotensin receptor-mediated blood pressure regulation in mice lacking both AT <sub>1A</sub> and AT <sub>1B</sub> receptors for angiotensin II

DOI Web Site 被引用文献21件
  • Michael I. Oliverio
    Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7524; and School of Pharmaceutical Sciences, University of Shizuoka, Yada Shizuoka-Shi, Japan
  • Hyung-Suk Kim
    Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7524; and School of Pharmaceutical Sciences, University of Shizuoka, Yada Shizuoka-Shi, Japan
  • Masaki Ito
    Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7524; and School of Pharmaceutical Sciences, University of Shizuoka, Yada Shizuoka-Shi, Japan
  • Thu Le
    Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7524; and School of Pharmaceutical Sciences, University of Shizuoka, Yada Shizuoka-Shi, Japan
  • Laurent Audoly
    Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7524; and School of Pharmaceutical Sciences, University of Shizuoka, Yada Shizuoka-Shi, Japan
  • Christopher F. Best
    Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7524; and School of Pharmaceutical Sciences, University of Shizuoka, Yada Shizuoka-Shi, Japan
  • Sylvia Hiller
    Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7524; and School of Pharmaceutical Sciences, University of Shizuoka, Yada Shizuoka-Shi, Japan
  • Kimberly Kluckman
    Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7524; and School of Pharmaceutical Sciences, University of Shizuoka, Yada Shizuoka-Shi, Japan
  • Nobuyo Maeda
    Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7524; and School of Pharmaceutical Sciences, University of Shizuoka, Yada Shizuoka-Shi, Japan
  • Oliver Smithies
    Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7524; and School of Pharmaceutical Sciences, University of Shizuoka, Yada Shizuoka-Shi, Japan
  • Thomas M. Coffman
    Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7524; and School of Pharmaceutical Sciences, University of Shizuoka, Yada Shizuoka-Shi, Japan

抄録

<jats:p> The classically recognized functions of the renin–angiotensin system are mediated by type 1 (AT <jats:sub>1</jats:sub> ) angiotensin receptors. Whereas man possesses a single AT <jats:sub>1</jats:sub> receptor, there are two AT <jats:sub>1</jats:sub> receptor isoforms in rodents (AT <jats:sub>1A</jats:sub> and AT <jats:sub>1B</jats:sub> ) that are products of separate genes ( <jats:italic>Agtr1a</jats:italic> and <jats:italic>Agtr1b</jats:italic> ). We have generated mice lacking AT <jats:sub>1B</jats:sub> ( <jats:italic>Agtr1b</jats:italic> −/−) and both AT <jats:sub>1A</jats:sub> and AT <jats:sub>1B</jats:sub> receptors ( <jats:italic>Agtr1a</jats:italic> −/− <jats:italic>Agtr1b</jats:italic> −/−). <jats:italic>Agtr1b</jats:italic> −/− mice are healthy, without an abnormal phenotype. In contrast, <jats:italic>Agtr1a</jats:italic> −/− <jats:italic>Agtr1b</jats:italic> −/− mice have diminished growth, vascular thickening within the kidney, and atrophy of the inner renal medulla. This phenotype is virtually identical to that seen in angiotensinogen-deficient ( <jats:italic>Agt</jats:italic> −/−) and angiotensin-converting enzyme-deficient ( <jats:italic>Ace</jats:italic> −/−) mice that are unable to synthesize angiotensin II. <jats:italic>Agtr1a</jats:italic> −/− <jats:italic>Agtr1b</jats:italic> −/− mice have no systemic pressor response to infusions of angiotensin II, but they respond normally to another vasoconstrictor, epinephrine. Blood pressure is reduced substantially in the <jats:italic>Agtr1a</jats:italic> −/− <jats:italic>Agtr1b</jats:italic> −/− mice and following administration of an angiotensin converting enzyme inhibitor, their blood pressure increases paradoxically. We suggest that this is a result of interruption of AT <jats:sub>2</jats:sub> -receptor signaling. In summary, our studies suggest that both AT <jats:sub>1</jats:sub> receptors promote somatic growth and maintenance of normal kidney structure. The absence of either of the AT <jats:sub>1</jats:sub> receptor isoforms alone can be compensated in varying degrees by the other isoform. These studies reaffirm and extend the importance of AT <jats:sub>1</jats:sub> receptors to mediate physiological functions of the renin–angiotensin system. </jats:p>

収録刊行物

被引用文献 (21)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ