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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)475-483
Number of pages9
JournalJournal of hypertension
Volume19
Issue number3
DOIs
Publication statusPublished - Jan 1 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Nakagawa, M., Tanaka, I., Mukoyama, M., Suga, S. I., Ogawa, Y., Tamura, N., Ishibashi, R., Goto, M., Nakagawa, O., Sugawara, A., & Nakao, K. (2001). Monoclonal antibody against brain natriuretic peptide and characterization of brain natriuretic peptide-transgenic mice. Journal of hypertension, 19(3), 475-483. https://doi.org/10.1097/00004872-200103000-00016