Monoclonal antibody against brain natriuretic peptide and characterization of brain natriuretic peptide-transgenic mice

Masayo Nakagawa, Issei Tanaka, Masashi Mukoyama, Shin Ichi Suga, Yoshihiro Ogawa, Naohisa Tamura, Rieko Ishibashi, Masahisa Goto, Osamu Nakagawa, Akira Sugawara, Kazuwa Nakao

研究成果: ジャーナルへの寄稿学術誌査読

4 被引用数 (Scopus)

抄録

Objective: Brain natriuretic peptide (BNP) is a ventricular hormone with natriuretic, diuretic and vasodilatory actions. Acute infusion of BNP reduces cardiac pre- and after-load in healthy and diseased subjects, but its long-term therapeutic usefulness remains unclear. Design: We prepared a monoclonal antibody specific to mouse BNP, and characterized transgenic mice overexpressing BNP in the liver (BNP-Tg mice) as a model of its chronic overproduction. Methods: Radioimmunoassay and neutralization experiments using the monoclonal antibody, KY-mBNP-I, were performed in BNP-Tg mice in conjunction with examinations of blood pressure (BP) and other markers for body fluid homeostasis. Results: We developed highly sensitive radioimmunoassay to mouse BNP. In BNP-Tg mice, the plasma BNP concentration increased more than 100-fold, while ventricular BNP concentration did not alter, suggesting that ventricular BNP production was not down-regulated in BNP-Tg mice. The BNP concentration in the kidneys was 10-fold higher than nontransgenic (nonTg) littermates, accompanied with marked reduction in the atrial natriuretic peptide (ANP) concentration, that may be due to binding of circulating BNP to the natriuretic peptide receptors. BNP-Tg mice showed significantly low arterial BP, and a bolus intraperitoneal administration of KY-mBNP-I completely abolished enhanced cGMP excretion in the urine and significantly increased the systolic BP. Conclusion: These results suggested that biological actions of BNP last and reduce cardiac overload in its long-term overproduction in the transgenic mouse model.

本文言語英語
ページ(範囲)475-483
ページ数9
ジャーナルJournal of hypertension
19
3
DOI
出版ステータス出版済み - 1月 1 2001
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 内科学
  • 生理学
  • 循環器および心血管医学

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